In vitro and in silico antibiofilm activity against methicillin-resistant Staphylococcus aureus of 2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone isolated from ethyl acetate fraction of Cleistocalyx operculatus

Journal: Revista Brasileira de Farmacognosia, WoS(SCIE), Q2
Author: Nguyễn Tấn Khanh - Trường Đại học Đông Á

Abstract:Biofilm formation by methicillin-resistant Staphylococcus aureus is one of the most important issues causing persistent infections and resistance to complete eradication with antibiotic therapy. The challenges in managing biofilms have spurred the discovery of new anti-infective drugs derived from natural resources. In this study, we aimed to investigate the antibacterial and antibiofilm activities of the ethyl acetate fraction and the chalcone 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone isolated from Cleistocalyx operculatus (Roxb.) Merr. et Perry, Myrtaceae, against a clinical isolate of methicillin-resistant Staphylococcus aureus. Our results revealed that at the minimum inhibitory concentration value of 100 µg/ml, the ethyl acetate fraction remarkably inhibited 90% of biofilm formation and disrupted nearly 50% of the mature biofilm of this pathogen. Additionally, 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone at subinhibitory concentrations of 100 and 50 µg/ml reduced methicillin-resistant Staphylococcus aureus biofilm formation by 50.54 and 36.59%, respectively. Molecular docking and kinetic simulations revealed that 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone binds stably to the active site of sortase A, a key enzyme required for Staphylococcus aureus to form biofilm, via Pi-sulfur interactions with two conserved residues, Cys184 and Arg197. Spectral analysis further confirmed that 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone binding alters the structural conformation of sortase A. Taken together, our study provides novel evidence that 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone isolated from the EtOAc fraction of C. operculatus could be a potential therapeutic candidate for combating methicillin-resistant Staphylococcus aureus infections. 

DOI: In vitro and in silico antibiofilm activity against methicillin-resistant Staphylococcus aureus of 2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone isolated from ethyl acetate fraction of Cleistocalyx operculatus | Revista Brasileira de Farmacognosia