Synthesis and evaluation of 2-(2-((4-substituted-phenoxy) methyl)-1H-benzo[d] imidazol-1-yl)acetohydrazone derivatives as antitumor agents

摘要

Twelve 2-(2-((4-substituted-phenoxy)methyl)-1H-benzo[d]imidazol- 1-yl)-acetylhydrazone derivatives were synthesized. These synthesized compounds have been tested for their antitumor activity in vitro against A549, MDA-MB-231, A375, and HCT116 cancer cells using the MTT assay. Among them, the compounds containing hydroxyl on position 2 at phenyl of hydrazone displayed a good anticancer activity, especially those containing two hydroxyl on 2 and 4 place at phenyl of hydrazone, for example, N'-(2,4-dihydroxybenzylidene)-2-(2-((p-tolyl-oxy)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide 7b, N'-(2,4-dihydroxybenzylidene)-2-(2-(phenoxymethyl)-1H-benzo[d]imidazol-1-yl) acetohydrazide 7f, 2-(2-((4-chlo-rophenoxy )methyl)-1H-benzo[d|imidazol-1 -yl)-N'-(2,4-di-hydroxybenzylidene)acetohydrazide 7j, have excellent antitumor activity. The results revealed that hydroxyl on position 2 at phenyl of hydrazone was necessary for anti-cancer activity, and another hydroxyl group on 4 place at phenyl can increase the inhibitory activity. An electron-withdrawing substituent at position 4 on phenyl ring of 2-phenoxylbenzimidazole was favorable to increasing anticancer activity toward MDA-MB-231, A375, and HCT116 cells.