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

  • Bioorg Med Chem. 2011 Apr 15;19(8):2565-81. doi: 10.1016/j.bmc.2011.03.015.
Ahmed Kamal  1 ,  M Kashi Reddy ,  M Janaki Ramaiah ,  Rajender ,  J Surendranadha Reddy ,  Y V V Srikanth ,  D Dastagiri ,  E Vijaya Bharathi ,  S N C V L Pushpavalli ,  Pranjal Sarma ,  Manika Pal-Bhadra
Affiliations
  • 1. Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad, India. [email protected]
PMID: 21459581 DOI: 10.1016/j.bmc.2011.03.015
Abstract

A series of new estradiol linked pyrrolo[2,1-c][1,4]benzodiazepine (E(2)-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.