In Vitro Antibreast Cancer and Anti-EGFR Studies of Some Novel Benzimidazole-Piperazine Containing 1,2,3-Triazoles

Abstract

Objective: Encouraged by the significant anticancer activities of benzimidazole, piperazine, and 1,2,3-triazole containing derivatives and based on the need for the development of new EGFR targeting antibreast cancer agents, our group now interested to synthesize new benzimidazole-piperazine-1,2,3-triazoles (VIIa–VIIn) as in vitro antibreast cancer and anti-EGFR agents. Methods: In this study, we focused on the synthesis of benzimidazole-piperazine-1,2,3-triazoles. As well, the in vitro antibreast cancer activity of compounds (VIIa–VIIn) against MDA-MB-231 and MCF-7 cell lines, and anti-EGFR activity of few compounds were studied via IC₅₀ values. Results and Discussion: Compounds (1-methyl-1H-benzo[d]imidazol-2-yl)(4-((1-(p-tolyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)methanone (VIIb), (4-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)metha none (VIIe), (4-((1-(3,5-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIh), and (4-((1-(4-chloro-3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone (VIIl) displayed higher activity against two cell lines than the Erlotinib. Furthermore, compounds (VIIb), (VIIe), and (VIIh) displayed greater inhibition against tyrosine kinase EGFR than the Erlotinib. The results of molecular docking studies of (VIIb), (VIIe), (VIIh), and (VIIl) as EGFR (PDB ID: 4HJO) targeting agents were found to be supportive with corresponding IC₅₀ data. Conclusions: We propose that mechanism of in vitro antibreast cancer activity of the investigated compounds, possibly will due to the tyrosine kinase EGFR inhibition.