Abstract
In an effort to establish new candidates with improved anticancer activity, we report here the synthesis of various series of N- substituted benzimidazole derivatives. The cytotoxicity of these compounds were determined using four cancer cell lines, A549 (human lung carcinoma cell line), MCF-7 (human breast adenocarcinoma cell line), HEP-G2 (human hepatocellular carcinoma cell line) and OVCAR-3 (human ovarian carcinoma cell line). Among the tested derivatives, there were 11 compounds (6c, 6d, 7a, 7b, 7c, 8a, 8c, 8d, 9a, 9b, 9c) possessing between 10.34 and 14.88 μM were lower than 16.04 μM (the IC50 value of cisplatin) for OVCAR-3 cells. Although most compounds examined were quite effective on A549, MCF-7 and OVCAR-3 cells, the compounds (E)-3-phenyl-1-(1-(2-(piperidin-1-yl)ethyl)-1H-benzo[d] imidazol-2-yl)prop-2-en-1-one (7a), (E)-3-phenyl-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one (8a) and (E)-1-(1-(3-morpholinopropyl)-1H- benzo[d]imidazol-2-yl)-3-phenylprop-2-en-1-one (9a) emerged as the most active compounds of this series. In particular, the compound 9a possessing great IC50 values on A549, MCF-7, HEP-G2 and OVCAR-3 cells showed in vitro cytotoxicity similar or even better than cisplatin. Additionally, compound 7a and 8a showed effective cytotoxicity on OVCAR-3 cells and arrested the cells at G2/M at a similar concentration of MTT experiment. Therefore, the result of flow cytometry showed that compound 7a and 8a have abilities to arrest cell cycle progression. In summary, we conclude that the novel series of N- substituted benzimidazole derivatives can serve as a prototype molecule for further development of a new class of anti-cancer agents.