The depsidones from marine sponge-derived fungus Aspergillus unguis IB151 as an anti-MRSA agent: Molecular docking, pharmacokinetics analysis, and molecular dynamic simulation studies
Dian Handayani, Ibtisamatul Aminah, Purnawan Pontana Putra, Andani Eka Putra, Dаyаr Аrbаin, Herland Satriawan, Mai Efdi, İsmail Çeli̇k, Trina Ekawati Tallei
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds 2-clorounguinol (1), unguinol (2), and nidulin (3), isolated from the marine sponge-derived fungus Aspergillus unguis IB1 both in vitro and in silico. The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count, respectively. The change in bacterial cell morphology was studied for the first time using scanning electron microscopy (SEM). In silico molecular docking, pharmacokinetics analysis, and molecular dynamic simulation were performed to determine possible protein-ligand interactions and stability of targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol (1). The research findings indicated that compounds 1 to 3 had MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA. The MRSA cells displayed a distinct shape after adding the depsidone compound, according to SEM. According to the in-silico study, 2-Chlorounguinol, has the highest binding affinity with PBP2a (-6.7 kcal/mol). As a comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a binding affinity of less than -6.6 kcal/mol. Based on the Lipinski rule of 5, depsidone compounds are a class of compounds with good pharmacokinetic properties, easily absorbed and permeable. These findings suggest that 2-Chlorounguinol has potential antibacterial activity and can be developed as an antibiotic adjuvant to reduce antimicrobial resistance.