title: Epoxide group relationship with cytotoxicity in withanolide derivatives from Withania somnifera.
abstract: Withania somnifera is one of the highly reputed medicinal plants of India. Its steroidal constituents exist in the form of two major substitution patterns, viz. withaferin A (1) and withanone (5). Withaferin A with oxidation at carbons 4, 5, and 6 is considered as an active type, especially as anticancer, whereas the withanones with oxidation at carbons 5, 6, and 7 rarely show any activity. We prepared a series of derivatives with modifications at carbons 5, 6, and 7 in ring B of these withanolides to study the role of the epoxide group towards the cytotoxic property of these bioactive steroids. We have converted withanolides into the respective thiiranes, amino alcohols and alcohols by selective reactions at the epoxide ring and were evaluated for in vitro anticancer activity against four cancer cell lines to study the structure activity relationships. The transformations of the epoxide group in withanolides of the withaferin A type showed moderate reduction in their cytotoxicity whereas the almost inactive withanones have shown some improvements in their alcohol derivatives.
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address: laxmisra@hotmail.com.
authors.forename: Laxminarain
authors.initials: L
authors.lastname: Misra
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Amreen A
authors.initials: AA
authors.lastname: Siddique
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Monica
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Shiv
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D032341:Withania / Q000737:chemistry*; D054358:Withanolides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; D054358:Withanolides; C560597:withanone; C009684:withaferin A
keywords: Amination; Cytotoxicity; Epoxide; Reduction; Withania somnifera; Withanolides