Jun’ichi Kobayashi

This book includes three reviews: on the chemistry of the secondary metabolites of termites ; on studies on isolation and structure elucidation of bioactive compounds in the life cycle of higher plants; and on Chemical Diversity and Biological Activity of African Propolis

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBioactive metabolites of symbiotic marine microorganismsJunichi. Kobayashi and Masami. IshibashiCite this: Chem. Rev. 1993, 93, 5, 1753–1769Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/cr00021a005RIGHTS & PERMISSIONSArticle Views2185Altmetric-Citations270LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-Alertsclose Get e-Alerts

Lycopodium alkaloids are unique heterocyclic alkaloids having C 11 N, C 15 N 2 , C 16 N, C 16 N 2 , C 22 N 2 , and C 27 N 3 types from genus Lycopodium and have attracted great interest from biogenetic and biological points of view as well as providing challenging targets for total synthesis. This review covered the structure elucidation and biological activity of new Lycopodium alkaloids and total synthesis of some Lycopodium alkaloids reported in the literature from 2004 to July in 2008.

About two hundred Daphniphyllum alkaloids have so far been isolated from thirteen species of the genus Daphniphyllum. This comprehensive review summarizes all the research into the isolation and structure elucidation of these alkaloids reported since investigations began in 1996. The structures of the Daphniphyllum alkaloids are classified based on six Daphniphyllum alkaloids (daphniphylline, secodaphniphylline, yuzurimine, daphnilactone A, daphnilactone B and yuzurine); these are also a number of newly found skeletons. The biosynthetic pathways, total syntheses, and bioactivities of the Daphniphyllum alkaloids are also described.

Tight junctions (TJs) create a paracellular permeability barrier and also act as a fence preventing intermixing of proteins and lipids between the apical and basolateral plasma membranes. Recently, claudin-1 has been identified as an integral membrane protein localizing at TJs, and introduced claudin-1 can form TJ-like networks in fibroblasts. To investigate the function of claudin-1, MDCK cells were transfected with a mammalian expression vector containing myc-tagged mouse claudin-1, and four stable clones were obtained. The myc-tagged claudin-1 precisely colocalized with both occludin and ZO-1 at cell-cell contact sites, indicating that exogenous claudin-1 was properly targeted to the TJs. Immunoblot analysis revealed that overexpression of claudin-1 increased expression of ZO-1 but not of occludin or ZO-2. The barrier functions of these cells were evaluated by transepithelial electrical resistance (TER) and paracellular flux. Claudin-1-expressing cells exhibited about four times higher TER than wild-type MDCK cells. Consistent with the increase of TER, the cells overexpressing claudin-1 showed reduced paracellular flux, estimated at 4 and 40 kD FITC-dextrans. These results suggest that claudin-1 is involved in the barrier function at TJs.

This review covers the structures, synthesis, biosynthesis, and bioactivity of a series of cytotoxic macrolides, named amphidinolides, isolated from symbiotic marine dinoflagellates of the genus Amphidinium which were separated from inside cells of marine flatworms. The structures of long-chain polyketides such as colopsinols isolated from Amphidinium sp. are also described.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEudistomins A-Q, .beta.-carbolines from the antiviral Caribbean tunicate Eudistoma olivaceumKenneth L. Rinehart Jr., Junichi Kobayashi, Gary C. Harbour, Jeremy Gilmore, Mark Mascal, Tom G. Holt, Lois S. Shield, and Francoise LafargueCite this: J. Am. Chem. Soc. 1987, 109, 11, 3378–3387Publication Date (Print):May 1, 1987Publication History Published online1 May 2002Published inissue 1 May 1987https://doi.org/10.1021/ja00245a031RIGHTS & PERMISSIONSArticle Views1562Altmetric-Citations198LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Marine microorganisms such as bacteria, cyanobacteria, dinoflagellates, and others have attracted many natural product chemists as the real producers of marine toxins such as fish and algal poisons as well as bioactive substances isolated from marine invertebrates such as sponges and tunicates. Among marine microorganisms, dinoflagellates have proved to be important sources of marine toxins and have been investigated worldwide by natural product chemists. We have continued investigations on chemically interesting and biologically significant secondary metabolites from Amphidinium spp., of a genus of symbiotic marine dinoflagellates separated from inside cells of Okinawan marine flatworms. This review covers the results described in our recent publications on a series of cytotoxic macrolides, designated amphidinolides, and long-chain polyketides isolated from Amphidinium spp. In this review, topics include the isolation, structure elucidation, synthesis, biosynthesis, and bioactivity of amphidinolides and long-chain polyketides.

Citrinadin A (2) is a pentacyclic indolinone alkaloid isolated from the cultured broth of a fungus, Penicillium citrinum, which was separated from a marine red alga. The absolute stereochemistry of the pentacyclic core in 2 and its new congener, citrinadin B (1), was elucidated by analysis of the ROESY spectrum for the chlorohydrin derivative (3) of 1 as well as comparison of the electronic circular dichroism (ECD) spectra for 1 and 2 with those of known spirooxiindole alkaloids. On the other hand, the absolute configuration at C-21 bearing an epoxide ring was assigned as S by comparison of the vibrational circular dichroism (VCD) spectra of 1 with those of model compounds 2S- and 2R-2,3-epoxy-3,3-dimethyl-1-phenylpropan-1-one (4a and 4b, respectively).

New bromotyrosine-derived alkaloids, purealidins B (1) and C (2), have been isolated from the Okinawan marine sponge Psammaplysilla purea and their structures elucidated on the basis of spectroscopic data. Purealidin B (1) showed antibacterial activity, while purealidin C (2) exhibited antifungal and antineoplastic activities.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEudistomins C, E, K, and L, potent antiviral compounds containing a novel oxathiazepine ring from the Caribbean tunicate Eudistoma olivaceumKenneth L. Rinehart, Junichi Kobayashi, Gary C. Harbour, Robert G Hughes Jr., Stephen A. Mizsak, and Terrence A. ScahillCite this: J. Am. Chem. Soc. 1984, 106, 5, 1524–1526Publication Date (Print):March 1, 1984Publication History Published online1 May 2002Published inissue 1 March 1984https://doi.org/10.1021/ja00317a079RIGHTS & PERMISSIONSArticle Views469Altmetric-Citations166LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (405 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlteramide A, a new tetracyclic alkaloid from a bacterium Alteromonas sp. associated with the marine sponge Halichondria okadaiHideyuki Shigemori, Myung Ae Bae, Kazunaga Yazawa, Takuma Sasaki, and Junichi KobayashiCite this: J. Org. Chem. 1992, 57, 15, 4317–4320Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue 1 July 1992https://doi.org/10.1021/jo00041a053RIGHTS & PERMISSIONSArticle Views1125Altmetric-Citations141LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (577 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Keramamine-A and -B, two new β-carboline alkaloids with a 13 membered ring have been isolated from the Okinawan marine sponge Pellina sp. as antimicrobial substances and the structures of keramamine-A and -B have been determined by X-ray analysis and by spectral and chemical means, respectively.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEudistomins A, D, G, H, I, J, M, N, O, P, and Q, bromo, hydroxy, pyrrolyl and iminoazepino .beta.-carbolines from the antiviral Caribbean tunicate Eudistoma olivaceumJunichi Kobayashi, Gary C. Harbour, Jeremy Gilmore, and Kenneth L. Rinehart Jr.Cite this: J. Am. Chem. Soc. 1984, 106, 5, 1526–1528Publication Date (Print):March 1, 1984Publication History Published online1 May 2002Published inissue 1 March 1984https://doi.org/10.1021/ja00317a080RIGHTS & PERMISSIONSArticle Views582Altmetric-Citations132LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (389 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

This review covers the recent results described in our publications on several new cytotoxic macrolides isolated from dinoflagellates of the genus Amphidinium in addition to an overview of the isolation, structure elucidation, synthesis, biosynthesis, and bioactivity of a series of cytotoxic macrolides, named amphidinolides, reported so far.

Abstract Background The presence of tumor‐infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). Methods We evaluated the associations between tumor‐infiltrating CD8 + T‐cell density and survival in five distinct compartments in 139 OSCC cases. Results There was a significant association between increased tumor‐infiltrating CD8 + T cells and their distribution. High parenchymal CD8 + T‐cell density at the invading tumor edge was associated with improved overall survival (OS) and disease‐specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8 + T‐cell density at the tumor periphery was also associated with improved recurrence‐free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8 + T‐cell density at the tumor periphery and high parenchymal CD8 + T‐cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18‐0.80 and 0.05‐0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively. Conclusions Assessment of CD8 + T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.

The three reviews cover the advances in the chemistry and biology of withanolides over the last 16 years, review the chemistry and biology of the rocaglamide-type derivatives and related compounds, wi

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p<0.01) and tumor budding (p<0.01) were associated with regional metastasis as well as lymphovascular invasion (p = 0.04) in univariate analysis. In logistic regression analysis, however, tumor budding was the only independent predictor of regional metastasis (hazard ratio (HR) = 3.05, 95% confidence interval (CI) = 0.29-5.30, p<0.01). All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survival (p<0.01, p = 0.03, and p<0.01, respectively) as well as lymphovascular invasion (p = 0.02) and perineural invasion (p = 0.02). A final model for Cox multivariate analysis identified the prognostic advantage of the intensity of tumor budding (HR = 2.19, 95% CI = 1.51-3.18, p<0.01) compared with the mode of invasion and WPOI in disease-free survival. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC. If the pancytokeratin-based immunohistochemical features of more than five buds, and a grade 4C or 4D mode of invasion are identified, careful wait-and-see follow-up in a short period with the use of imaging modalities is desirable. If there are more than ten buds, a grade 4D mode of invasion, or WPOI-5 in the same section, wide resection of the primary tumor with elective neck dissection should be recommended.

A novel manzamine-related alkaloid consisting of unprecedented 8/5/5/5/15/6 ring system, nakadomarin A (1), has been isolated from an Okinawan marine sponge Amphimedon sp., and the unique structure containing a furan ring was elucidated on the basis of the spectroscopic data. The relative stereochemistry was deduced from the NOE data and proton couplings, and a plausible biogenetic path of 1 through ircinal A was proposed.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIrcinals A and B from the Okinawan marine sponge Ircinia sp.: plausible biogenetic precursors of manzamine alkaloidsKazuhiko Kondo, Hideyuki Shigemori, Yumiko Kikuchi, Masami Ishibashi, Takuma Sasaki, and Junichi KobayashiCite this: J. Org. Chem. 1992, 57, 8, 2480–2483Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://doi.org/10.1021/jo00034a052Request reuse permissionsArticle Views1087Altmetric-Citations131LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (562 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

ChemInformVolume 35, Issue 52 Natural Products Citrinadin A, a Novel Pentacyclic Alkaloid from Marine-Derived Fungus Penicillium citrinum. Masashi Tsuda, Masashi Tsuda Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorYuu Kasai, Yuu Kasai Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorKazusei Komatsu, Kazusei Komatsu Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorTeruo Sone, Teruo Sone Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorMichiko Tanaka, Michiko Tanaka Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorYuzuru Mikami, Yuzuru Mikami Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorJun'ichi Kobayashi, Jun'ichi Kobayashi Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this author Masashi Tsuda, Masashi Tsuda Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorYuu Kasai, Yuu Kasai Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorKazusei Komatsu, Kazusei Komatsu Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorTeruo Sone, Teruo Sone Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorMichiko Tanaka, Michiko Tanaka Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorYuzuru Mikami, Yuzuru Mikami Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorJun'ichi Kobayashi, Jun'ichi Kobayashi Grad. Sch. Pharm. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this author First published: 01 December 2004 https://doi.org/10.1002/chin.200452182Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume35, Issue52December 28, 2004 RelatedInformation

A novel pentacyclic alkaloid, citrinadin A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from a marine red alga, and the structure was elucidated by spectroscopic data. The relative stereochemistry of the pentacyclic core was assigned on the basis of NOESY data and 1H−1H coupling constants, and the presence of an N,N-dimethyl-l-valine residue in 1 was determined by chiral HPLC analysis of the hydrolysate.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTManzacidins A-C, novel tetrahydropyrimidine alkaloids from the Okinawan marine sponge Hymeniacidon spJunichi Kobayashi, Fuyuko Kanda, Masami Ishibashi, and Hideyuki ShigemoriCite this: J. Org. Chem. 1991, 56, 14, 4574–4576Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://doi.org/10.1021/jo00014a052RIGHTS & PERMISSIONSArticle Views619Altmetric-Citations117LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (451 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Three new bicyclic peptides, celogentins A (1), B (2), and C (3), have been isolated together with a known-related peptide, moroidin (4), from the seeds of Celosia argentea, and their structures including absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins A (1), B (2), and C (3) inhibited the polymerization of tubulin, and celogentin C (3) was four times more potent than moroidin (4) in the inhibitory activity. Structure-activity relationship study using moroidin derivatives 5-7 and analogue 8 as well as celogentins A-C (1-3) and moroidin (4) indicates that the bicyclic ring system including unusual non-peptide connections among beta(s)-Leu, Trp, and His residues characteristic of celogentins and moroidin, with ring size and conformations suitable for interaction with tubulin would be important for their biological activity.

A new cyclic peptide with a 3-hydroxyoxindole ring, celogentin K (1), has been isolated from the seeds of Celosia argentea and the structure including its absolute stereochemistry was assigned by using extensive NMR, MS/MS, and CD spectra. The stereostructure of a known related bicyclic peptide, moroidin (2), was confirmed by a single crystal X-ray diffraction analysis.

A novel heteroaromatic substance, aaptamine possessing an α-adrenoceptor blocking activity has been isolated from the tropical sea sponge Aaptos aaptos and its structure has been determined to be 1 on the basis of spectral data and chemical degradation.

Two novel sphingosine-derived azetidine alkaloids, penaresidin A, 1a, and B, 1b, were isolated as potent actomyosin ATPase activators from the Okinawan marine sponge Penares sp. and the structures elucidated on the basis of spectral data, especially two-dimensional NMR spectra of their acetates.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEudistomidins B, C, and D: novel antileukemic alkaloids from the Okinawan marine tunicate Eudistoma glaucusJunichi Kobayashi, Jie Fei Cheng, Tomihisa Ohta, Shigeo Nozoe, Yasushi Ohizumi, and Takuma SasakiCite this: J. Org. Chem. 1990, 55, 11, 3666–3670Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://doi.org/10.1021/jo00298a056RIGHTS & PERMISSIONSArticle Views418Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (688 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Three bromopyrrole alkaloids, ageliferin (1), bromoageliferin (2), and dibromoageliferin (3), have been isolated as potent actomyosin ATPase activators from the Okinawan marine sponge Agelas sp. and the structures elucidated on the basis of spectral data, especially two dimensional NMR spectra.

Eight new dimeric bromopyrrole alkaloids, nagelamides A-H (1-8) and a monomeric one, 9,10-dihydrokeramadine (9), have been isolated from the Okinawan marine sponge Agelas sp., and the structures were elucidated from spectroscopic data. Nagelamides A-H (1-8) exhibited antibacterial activity against Gram-positive bacteria. Nagelamide G (7) inhibited protein phosphatase 2A activity.

The 270-MHz 1H and 68-MHz 13C nuclear magnetic resonance spectra of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Met-enkephalinamide are analyzed in a variety of solvents. For the dipolar form of Met-enkephalin in (C2H3)2SO solution, significant concentration dependences are found of C-alpha proton chemical shifts, indicating an aromatic ring-current effect in molecular aggregates. An anomalous temperature dependence is observed of the amide proton chemical shift of the Met-5 residue. Furthermore, the chemical shifts of C-alpha protons of the dipolar form are found to depend appreciably on temperature. From the analyses of the temperature dependences together with concentration dependences of C-alpha proton resonances, the dipolar form of Met-enkephalin is found to be in an equilibrium of folded and extended conformations at low concentration in (C2H3)2SO solution. Solvent-composition dependences of the amide and C-alpha proton resonances and carbonyl and alpha-carbon resonances of the dipolar form in 2H2O/(C2H3)2SO solution are consistent with the conformation equilibrium and the association equilibrium. The folded conformation of the dipolar form in (C2H3)2SO solution is stabilized by the intramolecular attraction between the positively charged N-terminal group and negatively charged C-terminal group. The presence of the folded conformation is confirmed by the measurements of Gd(III)-induced relaxation enhancements of C-alpha protons. Nuclear Overhauser effects on the dipolar form are not consistent with the predominant formation of the beta-turn structure with the intramolecular hydrogen bond (Gly-2) C=O . H-N(Met-5). For the dipolar form of Met-enkephalin in 2H2O solution and for the cationic form of Met-enkephalinamide in (C2H3)2SO solution and in 2H2O solution there is no evidence for the formation of folded conformations.

The awesome power of metathesis is illustrated by a concise synthesis of the extremely scarce marine natural product amphidinolide V, which hinges on a sequence of ring-closing alkyne metathesis followed by intermolecular enyne metathesis with ethylene (see scheme). As a complete set of conceivable stereoisomers was prepared, the constitution and absolute configuration of this macrolide could be established and first insights into structure-activity relationships governing its cytotoxicity were obtained.A sequence of ring-closing alkyne metathesis followed by an intermolecular enyne metathesis of the resulting cycloalkyne with ethene was used to forge the macrocyclic skeleton and to set the vicinal exo-methylene branches characteristic for the cytotoxic marine natural product amphidinolide V (1). Comparison of the synthetic material with an authentic sample of this extremely scarce metabolite isolated from a dinoflagellate of the Amphidinium sp. eliminated any doubts about its structure and allowed the absolute configuration of amphidinolide V to be determined as 8R,9S,10S,13R. Moreover, the flexibility inherent to the underlying synthesis blueprint also opened access to a comprehensive set of diastereomers of 1 as well as to synthetic analogues differing from the natural lead in the lipophilic chains appended to the macrocyclic core. This set of designed analogues gave first insights into structure-activity relationships, which revealed that the stereostructure of the macrolactone is a highly critical parameter, whereas the examined alterations of the side chain did not diminish the cytotoxicity of the compounds to any notable extent.

These peptides inhibit the contractile response of directly stimulated mouse diaphragm.

One of the major factors involved in the prognosis of oral squamous cell carcinoma (OSCC) patients is metastasis. Recent progress in cancer stem-like cell/cancer-initiating cell (CSC/CIC) research indicates that CSCs are related to metastasis. Aldehyde dehydrogenase 1 - (ALDH1) and SRY-related HMG-box gene 2 (SOX2) have recently been shown to be putative CSC markers for several human malignancies. The aim of this study was to determine the association of ALDH1 and SOX2 expression in oral squamous cell carcinoma (OSCC) with lymph node metastasis. Immunohistochemical staining of ALDH1, SOX2 and Ki67 was performed in 80 OSCC tissues. High expression rates of ALDH1 (2%-40%) were found to be related to lymph node metastasis (P = 0.0017). Interestingly, we found that SOX2 staining could be classified into two patterns: (i) peripheral staining pattern; and (ii) diffuse staining pattern. The diffuse staining pattern showed a significant correlation with lymph node metastasis (P < 0.001). No correlation was found between Ki67 staining and lymph node metastasis (P = 0.4724). The ALDH1 positive staining rates in metastatic lymph nodes were higher than that in corresponding primary OSCC tissues. These results indicate that high expression rates of ALDH1 and SOX2 diffuse staining patterns might be novel prediction markers for OSCC lymph node metastasis.

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTLyconadin A, a Novel Alkaloid from Lycopodium complanatumJun'ichi Kobayashi, Yusuke Hirasawa, Naotoshi Yoshida, and Hiroshi MoritaView Author Information Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan [email protected]Cite this: J. Org. Chem. 2001, 66, 17, 5901–5904Publication Date (Web):July 26, 2001Publication History Received16 April 2001Published online26 July 2001Published inissue 1 August 2001https://doi.org/10.1021/jo0103874Copyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1532Altmetric-Citations91LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (67 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbon,Chemical structure,Hydrocarbons,Organic compounds,Stereochemistry Get e-Alerts

Four new oxindole alkaloids, paratunamides A-D (1-4), containing a secologanin unit, were isolated from the bark of Cinnamodendron axillare, and their structures and relative configurations were elucidated by spectroscopic data. The absolute configuration at C-7 in 1-4 was assigned as S, S, R, and S, respectively, on the basis of the CD spectra.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCystodytins A, B, and C, novel tetracyclic aromatic alkaloids with potent antineoplastic activity from the Okinawan tunicate Cystodytes dellechiajeiJunichi Kobayashi, Jiefei Cheng, Markus R. Walchli, Hideshi Nakamura, Yoshimasa Hirata, Takuma Sasaki, and Yasushi OhizumiCite this: J. Org. Chem. 1988, 53, 8, 1800–1804Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April 1988https://doi.org/10.1021/jo00243a038Request reuse permissionsArticle Views468Altmetric-Citations82LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (654 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

[structure: see text] A novel Lycopodium alkaloid with an unprecedented fused-tetracyclic ring system consisting of an aza-cyclononane ring having a N-hydroxy group, a cyclohexanone, a cyclopentanone, and a tetrahydrofuran ring, sieboldine A (1), was isolated from the club moss Lycopodium sieboldii. The structure and relative stereochemistry were elucidated on the basis of 2D NMR data and X-ray analysis. Sieboldine A (1) exhibited a potent inhibitory activity against acetylcholinesterase and modest cytotoxicity.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmphidinolide C: the first twenty-five membered macrocyclic lactone with potent antineoplastic activity from the cultured dinoflagellate Amphidinium spJunichi. Kobayashi, Masami. Ishibashi, Markus R. Walchli, Hideshi. Nakamura, Yoshimasa. Hirata, Takuma. Sasaki, and Yasushi. OhizumiCite this: J. Am. Chem. Soc. 1988, 110, 2, 490–494Publication Date (Print):January 1, 1988Publication History Published online1 May 2002Published inissue 1 January 1988https://doi.org/10.1021/ja00210a029RIGHTS & PERMISSIONSArticle Views662Altmetric-Citations86LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (722 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Two types of Daphniphyllum alkaloids with unprecedented fused-hexacyclic ring systems, calyciphyllines A (1) and B (2), have been isolated from the leaves of Daphniphyllum calycinum (Daphniphyllaceae), and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data.

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.

A new pentacyclic oxindole alkaloid, speradine A (1), was isolated from the cultured broth of a fungus Aspergillus tamarii, which was separated from driftwood at a seashore in Okinawa. The structure and relative stereochemistry were determined by spectroscopic data and a single crystal X-ray diffraction analysis.

A novel bromine-containing pyrrole compound, hymenidin, has been isolated from the Okinawan marine spongeHymeniacidon sp. as a potent antagonist of serotonergic receptors and its structure elucidated using spectral data.

A novel alkaloid, prianosin A (1), with potent antineoplastic activity has been isolated from the Okinawan marine sponge Prianos melanos. Its absolute stereostructure was determined by single crystal x-ray diffraction analysis.

Three new taxoids, taxuspines A ∼ C (1 ∼ 3), possessing different skeletons from usual taxane diterpenoids consisting of a 6/8/6-membered ring system have been isolated together with known taxoids (4 ∼ 12) from stems of the Japanese yew Taxus cuspidata Sieb. et Zucc. and the structures elucidated on the basis of spectroscopic data. Most of the taxoids increased cellular accumulation of vincristine in multidrug-resistant tumor cells, while taxol (12) did not show such an activity. The taxoids (1 ∼ 11) showed no or weak cytotoxicity and among them, 2 and 6 reduced appreciably CaCI2-induced depolymerization of microtubules. These results suggest that some taxoids may be useful for overcoming multidrug resistance in tumor cells.

Ce@C82 is isolated by high-performance liquid chromatography (HPLC) and the cage symmetry is determined as C2v by measuring the 13C NMR spectra of its anion. The 13C NMR peaks of [Ce@C82]- show temperature-dependent shifts ascribed to the f electron remaining on the Ce atom. Both Ce@C82 and [Ce@C82]- are silent in electron spin resonance spectroscopy (ESR) because of the highly anisotropic g matrix as well as of the fast relaxation process originating from the orbital angular momentum of the f electron. This is the complementary relationship to the observation of the paramagnetic shift in 13C NMR. [Ce@C82]- has lower stability in air than [La@C82]-.

Two cytotoxic peptides, fellutamides A and B, have been isolated from the cultured fungus Penicillium fellutanum Biourge which was isolated from the gastrointestine of the marine fish Apogon endekataenia Bleeker, and the structures were elucidated to be 1 and 2 by two-dimensional NMR and FAB MS/MS data.

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C16N2 type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1–4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7–10.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrianosins B,C, and D, novel sulfur-containing alkaloids with potent antineoplastic activity from the Okinawan marine sponge Prianos melanosJie Fei Cheng, Yasushi Ohizumi, Markus R. Walchli, Hideshi Nakamura, Yoshimasa Hirata, Takuma Sasaki, and Junichi KobayashiCite this: J. Org. Chem. 1988, 53, 19, 4621–4624Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://doi.org/10.1021/jo00254a050RIGHTS & PERMISSIONSArticle Views241Altmetric-Citations70LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (540 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

A new cytotoxic bis-indole alkaloid, hyrtinadine A (1), with a pyrimidine moiety has been isolated from an Okinawan marine sponge Hyrtios sp., and the structure was elucidated on the basis of spectroscopic data.

A novel 20-membered macrolide, amphidinolide-A with antineoplastic activity has been isolated from the marine dinoflagellate Amphidinium sp. and its structure was determined to be 1 by spectral data.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIejimalides A and B, novel 24-membered macrolides with potent antileukemic activity from the Okinawan tunicate Eudistoma cf. rigidaJunichi Kobayashi, Jiefei Cheng, Tomihisa Ohta, Hideshi Nakamura, Shigeo Nozoe, Yoshimasa Hirata, Yasushi Ohizumi, and Takuma SasakiCite this: J. Org. Chem. 1988, 53, 26, 6147–6150Publication Date (Print):December 1, 1988Publication History Published online1 May 2002Published inissue 1 December 1988https://doi.org/10.1021/jo00261a040Request reuse permissionsArticle Views323Altmetric-Citations68LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (620 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Abstract A new pentacyclic quinone, xestoquinone was isolated from the Okinawan sea sponge Xestospongia sapra as a cardiotonic constituent and the structure was identified from its spectral data.

Novel pyridine alkaloids, theonelladins A ∼ D, with potent antileukemic activity have been isolated from the Okinawan marine sponge Theonella swinhoei and the structures elucidated on the basis of spectroscopic data.

A deposition simulator using the direct simulation Monte Carlo method has been developed to investigate deposition profile characteristics on small trenches in semiconductor manufacturing processes from vacuum to atmospheric pressure conditions. This simulator is applied to several deposition processes such as sputter deposition, plasma chemical vapor deposition, and atmospheric‐pressure chemical vapor deposition. Experimental results agree with simulator results concerning molecular collision, sticking coefficient, and appropriate surface‐reaction probability.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPseudodistomins A and B, novel antineoplastic piperdine alkaloids with calmodulin antagonistic activity from the Okinawan tunicate Pseudodistoma kanokoMasami Ishibashi, Yasushi Ohizumi, Takuma Sasaki, Hideshi Nakamura, Yoshimasa Hirata, and Junichi KobayashiCite this: J. Org. Chem. 1987, 52, 3, 450–453Publication Date (Print):February 1, 1987Publication History Published online1 May 2002Published inissue 1 February 1987https://doi.org/10.1021/jo00379a028RIGHTS & PERMISSIONSArticle Views265Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (592 KB) Get e-Alerts Get e-Alerts

A new bromine-containing alkaloid, keramadine, has been isolated from the Okinawan sea sponge Agelas sp. as a novel antagonist of serotonergic receptors and its structure has been elucidated by n.m.r. spectrometry.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) cytotoxic T lymphocytes (CTL). Survivin-2B80-88-specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro. We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin-2B80-88 peptide vaccination in HLA-A24-positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14-day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide-specific CTL frequency was detected in six of the eight patients evaluated by HLA-A24/peptide tetramer analysis. The present clinical trial revealed that survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN000000976.

Three new Lycopodium alkaloids, lyconadins D (1) and E (2), and complanadine E (3), were isolated from the club moss Lycopodium complanatum. Lyconadin D (1) was the first example of fastigiatine-type alkaloid isolated from Lycopodium complanatum. The structures and relative stereochemistry of 1-3 were elucidated on the basis of spectroscopic data. Complanadine E (3) enhanced mRNA expression for NGF.

Three new alkaloids, hyrtimomines A–C (1–3), were isolated from an Okinawan marine sponge Hyrtios sp. The structures of 1–3 were elucidated on the basis of spectroscopic analysis and application of a phenylglycine methyl ester (PGME) method. Hyrtimomines A (1) and B (2) are heteroaromatic alkaloids possessing a fused hexacyclic 6/5/6/6/7/5 ring system, while hyrtimomine C (3) is an alkaloid consisting of hydroxyindole and azepino-hydroxyindole moieties. Hyrtimomine A (1) exhibited cytotoxicity against KB and L1210 cells.

The first contribution reviews the phytochemical, chemical, and biological literature on members of the ingenane class of diterpenoids from their first isolation in 1968 through 2015, highlighting unr

Abstract Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues. We then validated their expression in 18 OSCC cell lines using qRT-PCR and identified 6 lncRNAs frequently overexpressed in OSCC. Among those, we found that knocking down DLEU1 (deleted in lymphocytic leukemia 1) strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion, and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC.

Natural products are well recognized as an important source of lead compounds in drug development. During the past >30 years, we have discovered >1000 novel bioactive natural products from Okinawan marine organisms (sponges, tunicates, cone shells, etc.) and microorganisms (fungi, bacteria, dinoflagellates, etc.). Some of them are used as bioprobes useful for basic studies of life sciences, while others are expected to be candidates of drug leads.

A novel tricyclic metabolite, brasilicardin A (1), with potent immunosuppressive activity has been isolated from the cultured broth of the actinomycete Nocardia brasiliensis IFM 0406, and the structure including absolute stereochemistry was established on the basis of spectroscopic data, chemical means, and X-ray analysis. Brasilicardin A (1) is the first tricyclic compound consisting of an anti/syn/anti-perhydrophenanthrene skeleton with a rhamnose, an N-acetylglucosamine, and an amino acid moiety.

Five new monoterpene indole alkaloids, naucleamides A-E (1-5), were isolated from the bark and wood of Nauclea latifolia, and the structures and relative stereochemistry were elucidated from the spectroscopic data. Naucleamide E (5) is a unique monoterpene indole alkaloid possessing a pentacyclic ring system with an amino acetal bridge.

Three novel quaternary indole alkaloids with an unprecedented 1-azoniatricyclo[4.3.3.01,5]undecane moiety, subincanadines A−C (1−3), as well as two new indole alkaloids with a 1-azabicyclo[5.2.2]undecane moiety, subincanadines D (4) and E (5), and a new indole alkaloid with a 1-azabicyclo[4.3.1]decane moiety, subincanadine F (6), have been isolated from the barks of Aspidosperma subincanum Mart, and the structures of 1−6 and the stereochemistry of 1−3 were elucidated by spectroscopic data and chemical means.

A unique bicyclic peptide, moroidin (1), from the seeds of Celosia argentea (Amaranthaceae) strongly inhibited the polymerization of tubulin. The stereostructure of moroidin (1) was reinvestigated by spectroscopic data, chemical degradation, and molecular dynamics simulation.

Keramaphidin B (1), a novel cytotoxic alkaloid possessing a 1,4-etheno-2,7-decahydronaphthylidine core with two macrocyclic rings has been isolated from an Okinawan marine sponge Amphimedon sp., and the structure was elucidated by extensive 2D NMR investigation as well as a single crystal X-ray analysis. Keramaphidin B (1) might be a plausible biogenetic precursor of manzamine alkaloids and a very important key compound to clarify the biogenetic path.

Eight highly modified Daphniphyllum alkaloids with unprecedented fused hexa- or pentacyclic skeletons, daphnicyclidins A-H (1-8), have been isolated from the stems of Daphniphyllum humile and D.teijsmanni, and their structures were elucidated on the basis of spectroscopic data and chemical means. The stereochemistry was elucidated by combination of NOESY correlations, X-ray crystallographic data, and CD analyses.

A new dimeric alkaloid with a lycodine-type skeleton, complanadine A (1), has been isolated from the club moss Lycopodium complanatum, and the structure including the absolute stereochemistry was elucidated on the basis of spectroscopic data.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmphidinolides G and H: new potent cytotoxic macrolides from the cultured symbiotic dinoflagellate Amphidinium spJunichi Kobayashi, Hideyuki Shigemori, Masami Ishibashi, Terufumi Yamasu, Hiroshi Hirota, and Takuma SasakiCite this: J. Org. Chem. 1991, 56, 17, 5221–5224Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://doi.org/10.1021/jo00017a044RIGHTS & PERMISSIONSArticle Views288Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (482 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Four new alkaloids, lycopladines B-D (1-3) and lyconadin B (4), have been isolated from the club moss Lycopodium complanatum and the structures including the stereochemistry were elucidated on the basis of spectral data and modified Mosher's method. Lyconadin B (4) elevated NGF mRNA expression in 1321N1 human astrocytoma cells.

A new cytotoxic compound, brasilibactin A (1), has been isolated from the actinomycete Nocardia brasiliensis IFM 0995, and the structure was elucidated on the basis of spectroscopic data and chemical means.

The actin-targeting toxins have not only proven to be invaluable tools in studies of actin cytoskeleton structure and function but they also served as a foundation for a new class of anticancer drugs. Here, we describe that amphidinolide H (AmpH) targets actin cytoskeleton. AmpH induced multinucleated cells by disrupting actin organization in the cells, and the hyperpolymerization of purified actin into filaments of apparently normal morphology in vitro. AmpH covalently binds on actin, and the AmpH binding site is determined as Tyr200 of actin subdomain 4 by mass spectrometry and halo assay using the yeast harboring site-directed mutagenized actins. Time-lapse analyses showed that AmpH stimulated the formation of small actin-patches, followed by F-actin rearrangement into aggregates via the retraction of actin fibers. These results indicate that AmpH is a novel actin inhibitor that covalently binds on actin.

A new dimer of C16N2 type alkaloid, complanadine B (1), and two new C16N type alkaloids, obscurumines A (2) and B (3), have been isolated from the club moss Lycopodium complanatum and L. obscurum, respectively. The structures and stereochemistry of 1–3 were elucidated by combination of 2D NMR spectra and chemical transformation. Complanadine A (4) isolated together with 1 induced secretion of neurotrophic factors from human astrocytoma cells.

Bromo-eudistomin D induced a contraction of the chemically skinned fibers from skeletal muscle at concentrations of 10 p~ or more.This contractile response to bromo-eudistomin D was completely blocked by 10 m M procaine.The extravascular ca2' concentrations of the heavy fractions of the fragmented sarcoplasmic reticulum (HSR) were measured directly by a Ca2' electrode to examine the effect of bromo-eudistomin D on the sarcoplasmic reticulum.After the HSR was loaded with Ca2+ by the ATP-dependent Ca2' pump, the addition of 10 p~ bromo-eudistomin D caused Ca2' release that was followed by spontaneous Ca" reuptake.In the presence of 2 p~ ruthenium red or 4 m M MgC12, no Ca2+ release was induced by 20 p~ bromoeudistomin D. The rate of 45Ca2' efflux from HSR, which had been passively preloaded with 46Ca2+ , was accelerated 7 times by 10 p~ bromo-eudistomin D. The concentration of bromo-eudistomin D for half-maximum effect on the apparent efflux rate was 1.5 PM, while that of caffeine was 0.6 m ~.The bromo-eudistomin D-evoked efflux of 46Ca2+ was abolished by 2 PM ruthenium red or 0.5 m M MgC12.Bromo-eudistomin D was found to be 400 times more potent than caffeine in its Ca2+-releasing action but was similar in its action in other respects.These results indicate that bromoeudistomin D may induce Ca2' release from the sarcoplasmic reticulum through physiologically relevant Ca2' channels. ~~An important problem in muscle biology concerns the mechanism which is involved in the excitation-contraction coupling between nerve and muscle.Especially lacking is knowledge of the mechanism whereby the sarcoplasmic reticulum (SR') releases Ca2+, which has been accumulated during muscle relaxation (1-3).Two major hypotheses have been postulated from work directed to the problem: either depolarization of the SR membrane induces Ca2+ release (3) or an

Two new indole alkaloids, hyrtiosins A (2) and B (3), together with known 5-hydroxyindole-3-aldehyde (1) have been isolated from the Okinawan marine sponge Hyrtios erecta and their structures elucidated on the basis of the spectroscopic data.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysiologically active marine natural products from Porifera. VIII. Agelasidines. Novel hypotaurocyamine derivatives from the Okinawan sea sponge Agelas nakamurai HoshinoHideshi Nakamura, Houming Wu, Junichi Kobayashi, Masaki Kobayashi, Yasushi Ohizumi, and Yoshimasa HirataCite this: J. Org. Chem. 1985, 50, 14, 2494–2497Publication Date (Print):July 1, 1985Publication History Published online1 May 2002Published inissue 1 July 1985https://doi.org/10.1021/jo00214a017RIGHTS & PERMISSIONSArticle Views274Altmetric-Citations62LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (594 KB) Get e-Alertsclose Get e-Alerts

New cyclic heptapeptides, hymenamides A and B, with a prolyproline segment have been isolated from the Okinawan marine sponge Hymeniacidon sp. and the structures elucidated on the basis of 2D NMR and FAB MS/MS data.

CD8(+) CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP(+) lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.

A novel tetracyclic alkaloid, perinadine A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structure was elucidated on the basis of spectroscopic data including 2D NMR spectra. Biogenetically, perinadine A (1) may be derived from citrinin (4), a well-known mycotoxin, and a scalusamide A-type pyrrolidine alkaloid.

Geographutoxin I1 (GTX 11), a peptide toxin isolated from Conus geographus, inhibited [3H]saxitoxin binding to receptor sites associated with voltage-sensitive Na channels in rat skeletal muscle homogenates and rabbit T-tubular membranes with K o .~ values of 6 0 .n ~ for homogenates and 35 n M for T-tubular membranes in close agreement with concentrations that block muscle contraction.Scatchard analysis of [3H]saxitoxin binding to T-tubular membranes gave values of KD = 9.3 n M and B,,, = 300 fmol/mg of protein and revealed

Novel diterpenes, agelasine-A, -B, -C, -D, -E, and -F were isolated from the Okinawan marine sponge Agelas nakamurai Hoshino and their structures were established to be monocyclic and bicyclic diterpenes having a 9-methyladeninium unit by spectral analyses and chemical transformations.

Eight stilbenoids, 1-(p-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (1), 2,7-dihydroxy-1,3-bis(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene (2), 4,7-dihydroxy-1-(p-hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene (3), 3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl (4), 3',5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (5), blestriarenes B (6) and C (7), and blestrianol A (8) have been isolated by the guidance of inhibitory effect of tubulin polymerization from the tubers of Bletilla striata (Orchidaceae). Among them, both of bisbenzyls 4 and 5 inhibited the polymerization of tubulin at IC(50) 10muM, respectively. Furthermore bisbenzyl 4 potentiated the cytotoxicity of SN-38 in BCRP-transduced K562 (K562/BCRP) cells.

Purealin , a novel secondary metabolite, which modurates enzymic reactions of ATPases, has been isolated from the okinawan marine sponge Psammaplysilla purea and the structure has been determined by the 1H-1H homonuclear and 1H-13C heteronuclear NMR chemical shift correlations and CD spectra.

Agelasine-E and -F, novel terpenoids with a 9-methyladeninium unit have been isolated from the orange colored sea sponge Agelas nakamurai Hoshino as Na,k-ATPase inhibitors and their structures and absolute configurations have been determined on the basis of spectral data and chemical conversions.

To evaluate pharmacokinetics and clinical efficacy of flomoxef (6315-S, FMOX) in neonates, FMOX was administered to 21 neonates. With 20 mg/kg and 40 mg/kg of intravenous drip-infusion of FMOX 60 minutes, half lives (T 1/2's) was 64.9 minutes and 130.3 minutes, respectively, and when 20 mg/kg of FMOX was infused intravenously to 2 cases, half lives were 70.8 minutes and 110.1 minutes, respectively. When 45-100 mg/kg of FMOX was administered to 17 neonates with infections (pneumonia 8, sepsis 1, sepsis suspected 2, intrauterine infection 2, urinary tract infection 2, omphalitis 2), the efficacy rate was 88.2% (15 of 17). No adverse reactions were observed clinically in the 21 neonates. Transient elevation of eosinophilia was observed in 1 case and transient elevation of S-GOT and S-GPT 1 in another. These results suggest that FMOX is an effective and safe antibiotic to use in neonates.

Eudistomidin-A, a novel indole alkaloid having calmodulin-antagonistic activity has been isolated from the Okinawan tunicate Eudistoma glaucus and the structure determined to be 1 on the basis of the spectral data and chemical derivatization.

A novel pyrrolopyrimidine alkaloid, rigidin (1), with calmodulin antagonistic activity has been isolated from the Okinawan marine tunicate Eudistoma cf. rigida. The structure was elucidated on the basis of spectral data of 1 and its pentamethyl derivative (2).

A potent cytotoxic 20-membered macrolide, iriomoteolide-1a (1), has been isolated from a benthic dinoflagellate Amphidinium sp. (strain HYA024), and the structure was elucidated on the basis of detailed analyses of 2-D NMR data. The relative and absolute stereochemistries were assigned by the combination of conformational analyses using NMR data and modified Mosher's method of 1.

A novel sesquiterpene, agelasidine-A possessing antispasmodic activity has been isolated from the sea sponge Agelas sp. and the structure has been determined on the basis of the spectral data and chemical degradation experiments.

A novel cytotoxic bis-3-alkylpyridine alkaloid with a β-amino acid moiety, nakinadine A (1), has been isolated from an Okinawan marine sponge Amphimedon sp., and the structure and stereochemistry were elucidated by spectroscopic data.

Two new tetracyclic prenylated acylphloroglucinols, chipericumins A (1) and B (2), were isolated from the roots of Hypericum chinense, together with two new tricyclic prenylated acylphloroglucinols, chipericumins C (3) and D (4). Their structures were elucidated by spectroscopic data. Chipericumins A-D (1-4) are prenylated acylphloroglucinols having a spiro skeleton with an acyl group, a methyl group, a C(5) unit, and a monoterpene moiety in common.

New Lycopodium alkaloids, lyconadins C (1) and F (2), were isolated from the club moss Lycopodium complanatum. Lyconadin C (1) is a new C16N2-type Lycopodium alkaloid possessing unique fused-tetracyclic ring system consisting of a cycloheptene ring fused to a decahydroquinoline and pyridone rings. Lyconadin F (2) possesses a primary amide moiety in its molecular, which is the first example of Lycopodium alkaloids. Biogenetically, lyconadins C (1) and F (2) might be related to lyconadins A (4) and B (5). The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute stereochemistry of 2 was elucidated by chemical correlations with lyconadin B (5) through hemiaminal form of lyconadin F (3).

Three new dimeric bromopyrrole alkaloids, nagelamides X–Z (1–3), were isolated from a marine sponge Agelas sp. Nagelamides X (1) and Y (2) possess a novel tricyclic skeleton consisting of spiro-bonded tetrahydrobenzaminoimidazole and aminoimidazolidine moieties. Nagelamide Z (3) is the first dimeric bromopyrrole alkaloid involving the C-8 position in dimerization. The structures of 1–3 were elucidated on the basis of spectroscopic data. Nagelamides X–Z (1–3) exhibited antimicrobial activity.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are considered to be essential for tumor maintenance, recurrence and metastasis. Therefore, eradication of CSCs/CICs is essential to cure cancers. However, the molecular mechanisms of CSCs/CICs are still elusive. In this study, we investigated the molecular mechanism of the cell growth of oral CSCs/CICs. Oral CSCs/CICs were isolated as aldehyde dehydrogenase 1 bright (ALDH1br) cells by the ALDEFLUOR assay. Small proline-rich protein-1B (SPRR1B) gene was shown to be overexpressed in ALDH1br cells by a cDNA microarray and RT-PCR. SPRR1B was shown to have a role in cell growth and maintenance of ALDH1br cells by SPRR1B overexpression and knockdown experiments. To elucidate the molecular mechanism by which SPRR1B regulates cell growth, further cDNA microarray analysis was performed using SPRR1B-overexpressed cells and cells with SPRR1B knocked down by siRNA. Expression of the tumor suppressor gene Ras association domain family member 4 (RASSF4) was found to be suppressed in SPRR1B-overexpressed cells. On the other hand, the expression of RASSF4 was enhanced in cells in which SPRR1B expression was knocked down by SPRR1B-specific siRNA. RASSF4 has an RA (Ras association) domain, and we thus hypothesized that RASSF4 modulates the MAP kinase signal downstream of the Ras signal. MAP kinase signal was activated in SPRR1B-overexpressed cells, whereas the signal was suppressed in SPRR1B knocked down cells. Taken together, the results indicate that the expression of SPRR1B is upregulated in oral CSCs/CICs and that SPRR1B has a role in cell growth by suppression of RASSF4.

Two structurally unique dimeric bromopyrrole alkaloids, agelamadins A (1) and B (2), were isolated from a marine sponge Agelas sp. Agelamadins A (1) and B (2) have a structure consisting of an agelastatin-like tetracyclic moiety and an oroidin-like linear moiety in common. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. The antimicrobial activity and cytotoxicity of agelamadins A (1) and B (2) were evaluated.

Nine new bromotyrosine alkaloids, purealidins J-R (1-9), have been isolated from the Okinawan marine sponge Psammaplysilla purea and the structures were elucidated on the basis of spectroscopic data. A hydroxy group as C-1 of purealidins M-O (4-6) may be biosynthetically derived from ring-opening of a spirocyclohexadienyl-isoxazole unit of purealidin J (1), aerophobin-1 (10), and purealidin L (3), respectively. Purealidins N (5), P (7), and Q (8) were cytotoxic to tumor cell lines, while purealidins J (1), K (2), P (7), and Q (8) showed moderate inhibitory activity against epidermal growth factor (EGF) receptor kinase.