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.