Synthesis of benzimidazole/triphenylamine-based compounds, evaluation of their bioactivities and an in silico study with receptor tyrosine kinases

Abstract

Benzimidazole (BI)/triphenylamine (TPA)-based compounds (AL-1 to AL-7) were synthesized and evaluated for their cytotoxic activity in different cell lines. Among them, AL-1 demonstrated good cytotoxic activity in all the chosen cell lines, as observed from the MTT results. The antiproliferative activity of AL-1 against various cancer cells indicates that this BI-TPA-based compound may be applicable as a potential multi-cancer inhibitor. AL-1 has a low IC₅₀ value for killing H446, demonstrating the efficacy of the selected BI-TPA derivatives against highly aggressive cancer cells (H446, small cell lung cancer—SCLC). The cytotoxicity performance is correlated with the presence of two redox peaks in the cyclic voltammetry (CV) analysis. It can be found from in silico analysis that AL-1 has a good Gscore towards the mutant receptor tyrosine kinase (RTK), PDGFRα. And it has a high stability for mutant EGFR (4RJ5) in a molecular dynamics simulation study. The small binding free energy from MM-GBSA is correlated with the formation of a stable complex structure. These studies suggest that BI-TPA-based compounds (e.g., AL-1) can be used as prospective anticancer agents to treat cancer cells and their mutant variants (resistant cancer cells).