In-silico and in-vitro study of hydroxythioxanthone derivatives as a potential candidate for antibacterial agents

A molecular docking study and molecular dynamics simulation were conducted to evaluate the inhibitory activity of hydroxythioxanthones against dihydrofolate reductase (DHFR) from Staphylococcus aureus and Bacillus subtilis proteins. The docking results showed that hydroxythioxanthones ( TX1 - TX4 ) had binding energies ranging from −7.25 to −7.76 kcal/mol and from −6.72 to −7.10 kcal/mol against these proteins. Compared to trimethoprim and Tetracycline, 1,3-dihydroxythioxanthone ( TX4 ) gave the lowest binding energy, implying that it forms tighter and potentially more effective interactions with dihydrofolate reductase (DHFR) Staphylococcus aureus and Bacillus subtilis proteins, which is remarkable. Additionally, molecular dynamics simulations over 100 ns confirmed that 1,3-dihydroxythioxanthone ( TX4 ) had better stability than other compounds, further supporting its potential as an effective antimicrobial agent against methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus subtilis strain M18 infections. Subsequently, all thioxanthones fulfill Lipinski's rule parameters. Among the hydroxythioxanthone derivatives, 1,3-dihydroxythioxanthone ( TX4 ) demonstrated remarkable antimicrobial activity against MRSA and Bacillus, with a low minimum inhibitory concentration (MIC) of 3.9 μg/mL. Based on in-silico and in-vitro studies, 1,3-dihydroxythioxanthone ( TX4 ) shows promise as an antibacterial drug candidate against methicillin-resistant Staphylococcus aureus (MRSA) and the Bacillus subtilis strain M18.