title: Ring A structural modified derivatives of withaferin A and the evaluation of their cytotoxic potential.
abstract: Regio-/stereoselective Michael addition to ring A of withaferin-A was performed using an optimized reaction procedure to synthesise a library of 2,3-dihydro,3-β-substituted withaferin-A derivatives. The analogues thus obtained were evaluated for in vitro cytotoxicity against various human cancer cell lines. 3-Azido analogue exhibited 35-fold increase (IC(50)=0.02-1.9 μM) in cytotoxicity against almost the entire cell lines tested when compared to the parent molecule. However, further modifications of 3-azido analogue with various alkynes under Husigen's cycloaddition conditions generated a variety of triazole derivatives with reduced cytotoxicity.
authors.affiliation: Natural Product Chemistry, Indian Institute of Integrative Medicine, Canal Road Jammu, 180001, India.
authors.forename: Syed Khalid
authors.initials: SK
authors.lastname: Yousuf
authors.forename: Rabiya
authors.initials: R
authors.lastname: Majeed
authors.forename: Mudassier
authors.initials: M
authors.lastname: Ahmad
authors.forename: Payare lal
authors.initials: Pl
authors.lastname: Sangwan
authors.forename: Basant
authors.initials: B
authors.lastname: Purnima
authors.forename: A K
authors.initials: AK
authors.lastname: Saxsena
authors.forename: K A
authors.initials: KA
authors.lastname: Suri
authors.forename: Debaraj
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Subhash Chandra
authors.initials: SC
authors.lastname: Taneja
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology; D054358:Withanolides / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D014230:Triazoles; D054358:Withanolides; C009684:withaferin A