Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity

Abstract

A novel series of N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinolines (14-33) containing triazole moiety were designed and synthesized through rational cycloadditions using the modified Pictet-Spengler reaction and the Click chemistry. Antiproliferative activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) revealed that many substituted triazole analogs of benzoates (20, 29) and benzaldehydes (30, 32) exhibited anticancer activity against all of the tested cancer cell lines in which the ester analog 20 was shown to be the most potent compound against HuCCA-1 (IC50= 0.63 μM) and A549 (IC50= 0.57 μM) cell lines. Triazoles bearing phenyl (15, 24), tolyl (26, 27), acetophenone (19), benzoate (20, 29), benzaldehyde (21, 30) and naphthalenyl (25) substituents showed stronger anticancer activity against HepG2 cells than that of the etoposide. Interestingly, the p-tolyl analog (27) displayed the most potent inhibitory activity (IC50= 0.56 μM) against HepG2 cells without affecting normal cells. Of the investigated tetrahydroisoquinoline-triazoles, the promising compounds 20 and 27 were selected for molecular docking against AKR1C3, which was identified to be a plausible target site. © 2014 Elsevier Masson SAS. All rights reserved.