Synthesis and biological evaluation of potent benzoselenophene and heteroaromatic analogues of (S) -1- (chloromethyl) -8-methoxy-2,3-dihydro-1H-benzo[e]indol-5-ol (seco-MCBI)
Mhetre, A.B.; Sreedhar, E.; Dubey, R.; Sable, G.A.; Lee, H.; Yang, H.; Lee, K.; Nam, D.-H.; Lim, D.
RSC Advances 9(50): 29023-29036
A diverse series of compounds (18a-x) were synthesized from (S)-1-(chloromethyl)-8-methoxy-2,3-dihydro-1H-benzo[e]indol-5-ol (seco-MCBI) and benzoselenophene or heteroaromatic acids. These new compounds were evaluated for their cytotoxicity against the human gastric NCI-N87 and human ovarian SK-OV3 cancer cell lines. The incorporation of a methoxy substituent at the C-7 position of the seco-CBI unit enhances the cytotoxicity through its additional van der Waals interaction and gave a much higher potency than the corresponding seco-CBI-based analogues. Similarly, the seco-MCBI-benzoselenophene conjugates (18h-x) exhibited substitution effects on biological activity, and the N-butyramido and N-methylthiopropanamido analogues are highly potent, possessing >77- and >24-fold better activity than seco-MCBI-TMI for the SK-OV3 and NCI-N87 cell lines, respectively.