Naturally Derived Malabaricone B as a Promising Bactericidal Candidate Targeting Multidrug-Resistant also Possess Synergistic Interactions with Clinical Antibiotics.

The emergence of multidrug-resistant (MDR) superbugs underlines the urgent need for innovative treatment options to tackle resistant bacterial infections. The clinical efficacy of natural products directed our efforts towards developing new antibacterial leads from naturally abundant known chemical structures. The present study aimed to explore an unusual class of phenylacylphenols (malabaricones) from as antibacterial agents. antibacterial activity was determined via broth microdilution, cell viability, time-kill kinetics, biofilm eradication, intracellular killing, and checkerboard assays. The efficacy was evaluated in murine neutropenic thigh and skin infection models. Confocal and SEM analyses were used for mechanistic studies. Among the tested isolates, malabaricone B () demonstrated the best activity against with a favorable selectivity index and concentration-dependent, rapid bactericidal killing kinetics. It displayed equal efficacy against MDR clinical isolates of and , efficiently clearing in intracellular and biofilm tests, with no detectable resistance. In addition, synergized with daptomycin and gentamicin. , exhibited significant efficacy against infection. Mechanistically, damaged membrane integrity, resulting in the release of extracellular ATP. The results indicated that can act as a naturally derived bactericidal drug lead for anti-staphylococcal therapy.