Abstract
The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC50 values 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 (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.
Highlights
In recent years benzimidazole derivatives have provided a large number of biologically active compounds that have been intensively used in medicinal chemistry as drugs
The 2-cyanomethylbenzo[c]imidazole (1) obtained from the reaction of ethyl cyanoacetate with o-phenylenediamine was used as the key starting material to synthesise biologically active heterocyclic derivatives
Compound 5 readily underwent bromination when treated with bromine in acetic acid solution at 60 oC to give the N-α-bromoacetylbenzo[c]imidazole derivative 6. The latter compound as α-bromocarbonyl compound showed interesting chemical reactivity when treated with some chemical reagents
Summary
In recent years benzimidazole derivatives have provided a large number of biologically active compounds that have been intensively used in medicinal chemistry as drugs. They are structural isosteres of naturally occurring nucleotides, which allow them to interact with the biopolymers of the living systems and various kinds of biological activities have been obtained. Some 2-aminobenzimidazoles display an appreciable antimicrobial effect Their corresponding carbamate derivatives have been synthesized for their significant in vivo antifilarial activity.[1] Concerning the high affinity that they display towards a variety of enzymes and protein receptors, they could be considered as pivotal structures in drug design.[2] Optimization of benzimidazole-based structures has resulted in marketed drugs, e.g. Omeprazole[3] and Pimobendan[4] that are therapeutically useful in the management of peptic ulcer and congestive heart failure, respectively.
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