Discovery of BI-10: An Unexplored Broad-Spectrum Antimicrobial Benzimidazole Derivative Targeting Bacterial Membrane.

Antimicrobial resistance (AMR) has emerged as a global healthcare crisis, necessitating the discovery of potent antibacterial agents. In the present investigation, we report the discovery, in vitro and ex vivo antibacterial efficacy studies, and mechanism of action of an unexplored benzimidazole derivative (BI-10), a promising broad-spectrum antibacterial agent with significant efficacy against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). BI-10 demonstrated a minimum Inhibitory Concentration (MIC) of 2.4 μg/ml (6.25 µM) against these priority pathogens. In vitro assessments revealed that BI-10 possessed rapid bactericidal activity, anti-biofilm potential and showed synergistic interactions with conventional antibiotics. Ex vivo efficacy studies using various mammalian cell lines demonstrated strong intracellular killing. Moreover, BI-10 showed the ability to prevent both adhesion and invasion of pathogens in different mammalian cell infection models. The membrane-disrupting nature of BI-10 against both pathogens was established using scanning electron microscopy, membrane permeability, depolarization, and integrity assays. Multiple in silico analyses further demonstrated drug-likeness and the biocompatibility profile of BI-10. Altogether, our findings establish BI-10 as a potent, broad-spectrum antimicrobial agent with robust in vitro and ex vivo efficacy and bacterial cell membrane-disrupting activity. This study highlights BI-10 as a valuable antibacterial lead molecule for the development of a new antimicrobial agent against multidrug-resistant pathogens.