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

A new class of estradiol-pyrrolobenzodiazepine conjugates have been prepared and evaluated for their anticancer activity. Further, some of the biological assays related to mechanism aspects have also been carried out. 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.