title: Antiproliferative withanolides from several solanaceous species.
abstract: To date, our work on solanaceous species (Datura wrightii, Jaborosa caulescens, Physalis hispida, Physalis longifolia, Vassobia breviflora and Withania somnifera) has resulted in the isolation of 65 withanolides, 31 of which were new, as well as the semi-synthesis of a further 30 withanolides. Structure identification and MTS assay-based antiproliferative evaluation of these 95 compounds revealed that a Δ(2)-1-oxo functionality in ring A, in conjunction with either a 5β,6β-epoxy or 5α-chloro-6β-hydroxy moiety in ring B, is the minimum structural requirement for withanolides to produce potent cytotoxic activity. Such structure-activity relationship analysis also revealed that oxygenation (the -OH or -OR groups) at C-4, 7, 11 and 12, as well as C-14 to C-28, did not contribute towards the observed antiproliferative activity. Herein, we present a complete overview of our work as it relates to the withanolides reported from 1965 to 2013.
authors.affiliation: a Department of Medicinal Chemistry , School of Pharmacy, University of Kansas , Lawrence , KS 66045 , USA.
authors.forename: Huaping
authors.initials: H
authors.lastname: Zhang
authors.forename: Cong-Mei
authors.initials: CM
authors.lastname: Cao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gallagher
authors.forename: Barbara N
authors.initials: BN
authors.lastname: Timmermann
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019657:Solanaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship; D054358:Withanolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D054358:Withanolides
keywords: Solanaceae; antiproliferative; cytotoxicity; structure–activity relationship; withanolide