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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

2019

ISSN/ISBN: 2046-2069
PMID: 35528410
DOI: 10.1039/c9ra04749b
Accession: 079912798
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.

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Related References

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