Abstract
The emergence of multidrug-resistant Acinetobacter baumannii poses a significant challenge in healthcare settings, highlighting the urgent need for new therapeutic strategies. This study investigates the inhibition potential of four natural compounds, epicatechin, quercetagetin, myricetin, and morin, against histidinol-phosphate aminotransferase (HPA), a key enzyme in the histidine biosynthesis pathway of A. baumannii. A comprehensive approach combining in silico simulations and experimental techniques was used to assess the efficacy of these compounds. The docking score for myricetin was -8.616 kcal/mol, while for morin, it was -8.082 kcal/mol. The in vitro results examined real-time binding interactions. Experimental validation using surface plasmon resonance (SPR) revealed dissociation constants of 2.6 × 10(-6) M for myricetin and 6.7 × 10(-6) M for morin, confirming their potent binding to the HPA enzyme. Also, the antibacterial activity was evaluated against A. baumannii using a minimum inhibitory concentration and growth curve analysis. The results showed that morin inhibited the growth of A. baumannii by more than 70% at its MIC value, whereas myricetin inhibited 50% of the bacteria at its MIC value. Based on these results, morin and myricetin were identified as the most promising inhibitors, displaying strong binding affinities, stable interactions, and favorable conformational dynamics. Thus, we conclude that both morin and myricetin can serve as potential inhibitors of AbHPA, forming the basis for a structure-based drug design against this deadly pathogen.