Design, synthesis and in vitro cytotoxicity studies of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-polyamide conjugates and 2,2 '-PBD dimers

A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-polyamide conjuga tes (1 and 2) and 2,2'-PBD dimers (3, 4 and 5) were synthesized and evaluat ed for cytotoxicity in >60 human tumor cell lines, In general PBD-polyamide conjugates (1 and 2) exhibit higher cytotoxic potency compared with 2,2-PB D dimers (3, 4 and 5), Compound 2 exhibits a wide spectrum of anticancer ac tivities against 17 cell lines in six cancer panels with LC50 values of <9 <mu>M, and is especially effective against colon cancer, melanoma, renal ca ncer and breast cancer, Compound 1 selectively affects cell growth against renal cancer A 498 cell line and compound 4 affects cell growth against bre ast cancer MDA-MB-231/ATCC cell line with an LC50 value 0.06 muM Increases in the chain length of the linker in 2,2'-PBD dimers significantly increase the cytotoxic potency and increases in the number of pyrrole groups in the PBD-polyamide conjugates similarly increase the cytotoxic potency.