Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]benzodiazepines as antimitotic agents

A series of new cinnamido-pyrrolo[2,1-c][1,4]benzodiazepine conjugates (4a–d and 5a–d) and their dimers (6a–d) have been designed, synthesized and evaluated for their biological activity. The anticancer screening of compound 4a by the NCI exhibited significant GI50 values ranging from 68 to 732 nM against 53 of 59 human cancer cell lines tested. Compounds 5a–d and 6a–d have also shown remarkable cytotoxic activity with GI50 values <0.1 μM concentrations in a large number of cell lines. Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in G0 and G2/M phase.

Graphical abstractA series of new cinnamido-pyrrolo[2,1-c][1,4]benzodiazepine conjugates and their dimers have been designed, synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects.Figure optionsDownload full-size imageDownload as PowerPoint slide