Synthetic studies on novel benzimidazolopeptides with antimicrobial, cytotoxic and anthelmintic potential

Abstract

Four substituted benzimidazolyl-benzoic/salicylic acids 5-8 were synthesized by interaction of 5,6-dimethyl-/6-nitrobenzimidazoles with diazotized substituted/unsubstituted aminobenzoic acids in the presence of cupric chloride. The coupling of compounds 5-8 with different amino acid ester hydrochlorides/dipeptide/tripeptide/tetrapeptide methyl esters afforded novel benzimidazolopeptide derivatives 5a-f, 6a-h, 7a-g and 8a-g. The structures of all newly synthesized compounds were established on the basis of analytical, IR, (1)H NMR, (13)C NMR and mass spectral data. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to yield corresponding acid derivatives 5b(a)-d(a), 6e(a)-g(a), 7c(a)-e(a) and 8e(a)-g(a). All peptide derivatives were screened for their antimicrobial, anthelmintic and cytotoxic activities. Almost all newly synthesized benzimidazolopeptides have shown moderate to good anthelmintic activity against all three earthworm species and good antimicrobial activity against pathogenic fungal strains Candida albicans and Aspergillus niger, gram negative bacterial strains Pseudomonas aeruginosa and Escherichia coli. Compounds 8g and 8g(a) possessed significant cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.