Minor withanolides of Physalis longifolia: structure and cytotoxicity. Zhang, H., Motiwala, H., Samadi, A., Day, V., Aubé, J., Cohen, M., Kindscher, K., Gollapudi, R., & Timmermann, B. Chemical & Pharmaceutical Bulletin, 60(10):1234–1239, 2012. doi abstract bibtex In our recent publication on bioactive guided isolation of compounds from Physalis longifolia (Solanaceae) novel anti-proliferative agents withalongolides A (4) and B (5), and their highly cytotoxic analogues, withalongolide A 4,19,27-triacetate (4a) and withalongolide B 4,19-diacetate (5a) were elucidated. In this study, the two lead compounds (4, 5) were re-isolated in gram quantities for the purpose of further analogue preparation and in vivo testing that would continue to probe structure-activity relationships. During this process, two additional withanolides, named withalongolides O (1) and P (2), were elucidated. Their structures were determined by spectroscopic techniques with 1 being subsequently confirmed by X-ray crystallographic analysis. Utilizing a MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] viability assay, withalongolide O (1) and its 4,7-diaceatate (1a), both containing the functionalities of Δ(2)-1-oxo- in A ring, a 5β,6β-epoxy in B ring, and a lactone ring in the nine-carbon side chain, exhibited potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal lung fibroblast (MRC-5) cells with IC(50) values in the range between 0.15 and 2.95 µM. In addition, the previously reported α orientation of 7-acetate group in acnistins C and D should be revised to the β orientation on the basis of NMR data comparison.
@article{zhang_minor_2012,
title = {Minor withanolides of {Physalis} longifolia: structure and cytotoxicity},
volume = {60},
issn = {1347-5223},
shorttitle = {Minor withanolides of {Physalis} longifolia},
doi = {10.1248/cpb.c12-00305},
abstract = {In our recent publication on bioactive guided isolation of compounds from Physalis longifolia (Solanaceae) novel anti-proliferative agents withalongolides A (4) and B (5), and their highly cytotoxic analogues, withalongolide A 4,19,27-triacetate (4a) and withalongolide B 4,19-diacetate (5a) were elucidated. In this study, the two lead compounds (4, 5) were re-isolated in gram quantities for the purpose of further analogue preparation and in vivo testing that would continue to probe structure-activity relationships. During this process, two additional withanolides, named withalongolides O (1) and P (2), were elucidated. Their structures were determined by spectroscopic techniques with 1 being subsequently confirmed by X-ray crystallographic analysis. Utilizing a MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] viability assay, withalongolide O (1) and its 4,7-diaceatate (1a), both containing the functionalities of Δ(2)-1-oxo- in A ring, a 5β,6β-epoxy in B ring, and a lactone ring in the nine-carbon side chain, exhibited potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal lung fibroblast (MRC-5) cells with IC(50) values in the range between 0.15 and 2.95 µM. In addition, the previously reported α orientation of 7-acetate group in acnistins C and D should be revised to the β orientation on the basis of NMR data comparison.},
language = {eng},
number = {10},
journal = {Chemical \& Pharmaceutical Bulletin},
author = {Zhang, Huaping and Motiwala, Hashim and Samadi, Abbas and Day, Victor and Aubé, Jeffrey and Cohen, Mark and Kindscher, Kelly and Gollapudi, Rao and Timmermann, Barbara},
year = {2012},
pmid = {23036966},
pmcid = {PMC3762585},
keywords = {Antineoplastic Agents, Phytogenic, Carcinoma, Squamous Cell, Cell Line, Cell Line, Tumor, Cell Survival, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Head and Neck Neoplasms, Humans, Melanoma, Models, Molecular, Physalis, Squamous Cell Carcinoma of Head and Neck, Structure-Activity Relationship, Withanolides},
pages = {1234--1239},
}
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In this study, the two lead compounds (4, 5) were re-isolated in gram quantities for the purpose of further analogue preparation and in vivo testing that would continue to probe structure-activity relationships. During this process, two additional withanolides, named withalongolides O (1) and P (2), were elucidated. Their structures were determined by spectroscopic techniques with 1 being subsequently confirmed by X-ray crystallographic analysis. Utilizing a MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] viability assay, withalongolide O (1) and its 4,7-diaceatate (1a), both containing the functionalities of Δ(2)-1-oxo- in A ring, a 5β,6β-epoxy in B ring, and a lactone ring in the nine-carbon side chain, exhibited potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal lung fibroblast (MRC-5) cells with IC(50) values in the range between 0.15 and 2.95 µM. In addition, the previously reported α orientation of 7-acetate group in acnistins C and D should be revised to the β orientation on the basis of NMR data comparison.","language":"eng","number":"10","journal":"Chemical & Pharmaceutical Bulletin","author":[{"propositions":[],"lastnames":["Zhang"],"firstnames":["Huaping"],"suffixes":[]},{"propositions":[],"lastnames":["Motiwala"],"firstnames":["Hashim"],"suffixes":[]},{"propositions":[],"lastnames":["Samadi"],"firstnames":["Abbas"],"suffixes":[]},{"propositions":[],"lastnames":["Day"],"firstnames":["Victor"],"suffixes":[]},{"propositions":[],"lastnames":["Aubé"],"firstnames":["Jeffrey"],"suffixes":[]},{"propositions":[],"lastnames":["Cohen"],"firstnames":["Mark"],"suffixes":[]},{"propositions":[],"lastnames":["Kindscher"],"firstnames":["Kelly"],"suffixes":[]},{"propositions":[],"lastnames":["Gollapudi"],"firstnames":["Rao"],"suffixes":[]},{"propositions":[],"lastnames":["Timmermann"],"firstnames":["Barbara"],"suffixes":[]}],"year":"2012","pmid":"23036966","pmcid":"PMC3762585","keywords":"Antineoplastic Agents, Phytogenic, Carcinoma, Squamous Cell, Cell Line, Cell Line, Tumor, Cell Survival, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Head and Neck Neoplasms, Humans, Melanoma, Models, Molecular, Physalis, Squamous Cell Carcinoma of Head and Neck, Structure-Activity Relationship, Withanolides","pages":"1234–1239","bibtex":"@article{zhang_minor_2012,\n\ttitle = {Minor withanolides of {Physalis} longifolia: structure and cytotoxicity},\n\tvolume = {60},\n\tissn = {1347-5223},\n\tshorttitle = {Minor withanolides of {Physalis} longifolia},\n\tdoi = {10.1248/cpb.c12-00305},\n\tabstract = {In our recent publication on bioactive guided isolation of compounds from Physalis longifolia (Solanaceae) novel anti-proliferative agents withalongolides A (4) and B (5), and their highly cytotoxic analogues, withalongolide A 4,19,27-triacetate (4a) and withalongolide B 4,19-diacetate (5a) were elucidated. 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