Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors

Abstract

A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.

Pyrrolo[2,1-a]isoquinoline scaffolds for developing anti-cancer agents

“…New 1,4-disubstituted-3,4-dihydroisoquinoline derivatives 123 were synthesized using the amidation reaction of substituted 2-arylethylamines 120 and benzoic acids derivatives 121a to give substituted benzamides 122 and their subsequent Bischler–Napieralski cyclization which afforded the desired isoquinoline products 123 in good yields (Scheme 9). 59…”