In vitro Anticancer Activities of Compounds Containing a Benzimidazole Core and In Silico Pharmacokinetic–Toxicity Analyses

Benzimidazole-based compounds are widely recognized as versatile scaffolds in drug discovery due to their structural diversity and broad spectrum of biological activities, including anticancer effects. Breast cancer remains one of the most prevalent malignancies among women worldwide, and the high incidence, mortality rates, and emergence of resistance to current therapies highlight the need for safer and more effective treatment strategies. In this study, two different compounds containing a benzimidazole core (3a and 3b) were prepared, and the structure of the new compound (3b) was characterized using spectroscopic methods. The cytotoxic activities of 3a and 3b were comprehensively evaluated in vitro using two breast cancer cell lines (MCF-7 and MDA-MB-231). The results revealed concentration-dependent cytotoxic effects, with compound 3a showing higher activity against the MCF-7 cell line (IC₅₀ = 88.15 µM) compared to MDA-MB-231 cells (IC₅₀ = 145.80 µM). The pharmacokinetic and toxicological properties of 3a and 3b were predicted using in silico approaches. ADMET analyses and BOILED-Egg model results indicated that compounds 3a and 3b have good oral absorption potential and the possibility of crossing the blood-brain barrier. In silico toxicity assessments revealed that both compounds have an inactive profile in terms of hepatotoxicity, nephrotoxicity, and cardiotoxicity; however, they should be carefully evaluated for neurotoxicity and mutagenicity. Furthermore, based on acute oral toxicity estimates, the LD₅₀ values of the compounds were calculated to be approximately 400 mg/kg, and the toxicity class was determined to be 4.