Novel Benzimidazole‐Urea Phenylalanine Hybrids as Dual‐Acting Antimicrobial and Anticancer Agents: In Silico and Biological Evaluation

The emergence of multidrug-resistant microorganisms and the limited therapeutic options for hepatocellular carcinoma (HCC) highlight the urgent need for new molecular scaffolds with dual pharmacological potential. In this study, a novel series of benzimidazole-urea phenylalanine hybrids was designed and synthesized using a rational structure-based approach to integrate antimicrobial and anticancer functionalities within a single pharmacophore. All synthesized compounds were characterized by spectroscopic methods and evaluated for their antimicrobial and cytotoxic activities. Among the series, CPN305 exhibited the most potent cytotoxicity against hepatocellular carcinoma cell lines (PLC/PRF/5 and HuH7) while maintaining minimal toxicity toward normal human fibroblasts (BJ-1). Additionally, the compound demonstrated promising antimicrobial efficacy against Staphylococcus aureus. Molecular docking simulations revealed favorable binding interactions within the Hsp90 active site, supporting the observed in vitro anticancer effects, while ADME predictions indicated desirable physicochemical and pharmacokinetic properties. Collectively, these findings suggest that the benzimidazole-urea phenylalanine scaffold represents a promising lead framework for further structural optimization and mechanistic exploration as a dual-acting antimicrobial and anticancer agent.