Abstract
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-tolyloxy)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-chlorophenoxy)methyl)-1H-benzo[d]imidazol-1-yl)-N′-(2,4-dihydroxybenzylidene)acetohydrazide 7j, have excellent antitumor activity. The results revealed that hydroxyl on position 2 at phenyl of hydrazone was necessary for anticancer 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.
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Acknowledgments
The authors thank the Analytical and Testing Center of West China Medical College, Sichuan University for 1H NMR, 13C NMR, MS, IR, and the Analytical and Testing Center of Chengdu institute of organic chemistry for elemental analysis.
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Li, Z., Zhang, S., Deng, L. et al. Synthesis and evaluation of 2-(2-((4-substituted-phenoxy)methyl)-1H-benzo[d] imidazol-1-yl)acetohydrazone derivatives as antitumor agents. Med Chem Res 23, 4050–4059 (2014). https://doi.org/10.1007/s00044-014-0981-5
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DOI: https://doi.org/10.1007/s00044-014-0981-5