New approaches for the synthesis, cytotoxicity and toxicity of heterocyclic compounds derived from 2-cyanomethyl benzo[c]imidazole

Abstract

The reaction of ethyl cyanoacetate 2 with o-phenylenediamine 1 gave the 2-cyanomethylbenzo[c]imidazole 3. The latter compound was used as the key starting material to synthesis biologically active heterocyclic derivatives. Thus, the reaction of compound 3 with cyclohexanone 4 and either of benzaldehyde (5a), 4-methoxybenzaldehyde (5b) or 4-chlorobenzaldehyde (5c) gave the annulated derivatives 6a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breastadeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 6b, 12, 22b, 22c, 25, 32, 33 and 35 exhibited optimal cytotoxic effect against cancer cell lines, with IC50’s in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals’ in vivo lethality to shrimp larvae (Artemiasalina), Brine-Shrimp Lethality Assay was used. Compounds 22b, 25 and 33 showed non toxicity against the tested organisms.

Keywords

• benzimidazole
• thiophene
• thiazole
• synthesis
• anti-tumor
• toxicity