Synthesis and biological evaluation of potent benzoselenophene and heteroaromatic analogues of ( S )-1-(chloromethyl)-8-methoxy-2,3-dihydro-1 H -benzo[ e ]indol-5-ol ( seco -MCBI)

A diverse series of compounds (18a-x) were synthesized from ( )-1-(chloromethyl)-8-methoxy-2,3-dihydro-1 -benzo[ ]indol-5-ol ( -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 -CBI unit enhances the cytotoxicity through its additional van der Waals interaction and gave a much higher potency than the corresponding -CBI-based analogues. Similarly, the -MCBI-benzoselenophene conjugates (18h-x) exhibited substitution effects on biological activity, and the -butyramido and -methylthiopropanamido analogues are highly potent, possessing >77- and >24-fold better activity than -MCBI-TMI for the SK-OV3 and NCI-N87 cell lines, respectively.