Synthesis of Novel 6-Acylamino-Benzimidazole Derivatives Derived from Carbendazim

Abstract

Benzimidazole derivatives possess potential biological activity, and modern methods are required for the synthesis of new derivatives in high yields. The aim of this study was to obtain new benzimidazole derivatives through acylation of carbendazim (1) with aliphatic carboxylic acids, then carry out the reactions of nitration, reduction and acylation of acyl-derivatives, and studying chemical structure and cytotoxic activity of the obtained compounds. The resulting acyl compounds (2 and 3) were nitrated to synthesize 6-nitro derivatives (4 and 5) in high yields. Their reduction gave 6-aminobenzimidazole derivatives (6 and 7), respectively. The yield of the synthesized compound (6) was 72.1%, and that of compound (7) was 93%. Compounds (6) and (7) were acylated with aliphatic carboxylic acids to obtain bis-acyl products. It is worth noting that selective acylation of the amino group at position 6 of the benzimidazole molecule led to the formation of amides (8-14) in 79-92% yields. Only the reaction of compound (6) with glacial acetic acid led to the formation of triacetamide (8) in 92% yield. The synthesized all compounds were characterized by ¹H, ¹³C NMR, IR spectral data. Additionally, synthesized benzimidazole derivatives were evaluated for their cytotoxic activity against triple-negative breast cancer cell lines (BT-20, MDA-MB-231, HCC1395) and the noncancerous HEK293 line using the MTT assay. Most compounds showed low cytotoxicity (IC₅₀ > 50 μM), while derivatives (9) and (10) exhibited moderate activity suggesting that the presence of ethyl (9) or propyl (10) groups at position 2 of the imidazole ring influences the anticancer potential.