Synthesis and biological evaluation of estradiol linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates as potential anticancer agents

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• 作者：Ahmed Kamal ; ^a ; ^{ahmedkamal@iict.res.in} ; M. Kashi Reddy^a ; M. Janaki Ramaiah^a ; Rajender^a ; J. Surendranadha Reddy^a ; Y.V.V. Srikanth^a ; D. Dastagiri^a ; E. Vijaya Bharathi^a ; S.N.C.V.L. Pushpavalli^a ; Pranjal Sarma^a ; Manika Pal-Bhadra ; ^a ; ^{manika@iict.res.in}
• 关键词：Pyrrolobenzodiazepine ; Estradiol ; Anticancer agents ; Tubulin polymerisation ; Apoptosis ; Tunel assay ; p53 ; p21 ; HDACs
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：15 April 2011
• 年：2011
• 卷：19
• 期：8
• 页码：2565-2581
• 全文大小：1552 K

文摘

A series of new estradiol linked pyrrolo[2,1-c][1,4]benzodiazepine (E₂-PBD) conjugates (3a–f, 4a–f and 5a–f) with different linker architectures including a triazole moiety have been designed and synthesized. All the 18 compounds have been evaluated for their anticancer activity and it is observed that some of the compounds particularly 4c–e and 5c,d exhibited significant anticancer activity. The detailed biological aspects relating to the cell cycle effects and tubulin depolymerization activity have been examined with a view to understand the mechanism of action of these conjugates. Among all these conjugates, one of the compound 5c could be considered as the most effective compound particularly against MCF-7 breast cancer cell line.