Antibacterial and Potentiating Activity of 3-Methoxycinnamic Acid on Antibiotics: An In Vitro and In Silico Approach

Antimicrobial resistance is a global health threat driven by mechanisms like biofilm formation and efflux pumps. This study evaluated the antibacterial activity, antibiotic-modulating potential, and pharmacokinetic properties of 3-methoxycinnamic acid (3MCA) using in vitro and in silico methods. Although 3MCA showed no direct antibacterial effect (MIC > 512 μg/mL), it enhanced the efficacy of gentamicin against multidrug-resistant (MDR) E. coli (60.3% MIC reduction) and ampicillin against MDR S. aureus (37% reduction). ADMET analysis revealed good drug-like properties, low intestinal absorption, no interaction with P-glycoprotein, and effective blood–brain barrier penetration, but potential toxicological risks such as hepatotoxicity. Molecular docking showed moderate binding affinities to target proteins through stable hydrogen bonds and aromatic interactions. These results suggest that 3MCA may act as an antibiotic resistance modulator, although further in vivo studies are necessary to confirm its safety and therapeutic potential.