Synthesis and Biological Evaluation of Chromene Derivatives as Carbapenem Adjuvants Against MRSA

Abstract

The increasing prevalence of antimicrobial resistance has stimulated interest in non-antibiotic small molecules that can restore or potentiate the activity of established antibacterial agents. In this study, a focused series of low-molecular-weight chromene derivatives was synthesized, structurally characterized, and evaluated primarily as antibacterial adjuvants rather than as stand-alone antibiotics. The experimental strategy was designed to distinguish intrinsic antibacterial activity from potentiating activity in combination with a partner antibiotic. Initial susceptibility testing was followed by combination experiments in selected bacterial strains, with particular emphasis on changes in the minimum inhibitory concentration (MIC) of meropenem or doripenem in the presence of each test compound. Broth microdilution combination assays demonstrated that compound 3a significantly reduced the MIC of meropenem and doripenem against methicillin-resistant Staphylococcus aureus (MRSA). The observed adjuvant effect suggests that chromene scaffolds may serve as promising candidates for the development of next-generation β-lactam enhancers aimed at overcoming carbapenem resistance.