Virtually screened novel sulfathiazole derivatives as a potential drug candidate for methicillin-resistant...

Area of Science:

• Medicinal Chemistry
• Computational Drug Discovery
• Antimicrobial Research

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant tuberculosis (MDR-TB) pose significant global health threats, driving the need for novel antimicrobial agents.
• Existing treatments face challenges due to rising resistance, necessitating innovative therapeutic strategies.

Purpose of the Study:

• To design and virtually screen novel sulfathiazole derivatives as potential agents against MRSA and MDR-TB.
• To evaluate the drug-likeness and pharmacokinetic properties of identified lead compounds.

Main Methods:

• Utilized BIOVIA Discovery Studio 2017 for virtual screening of 74 designed sulfathiazole compounds against MRSA and MDR-TB targets.
• Performed molecular docking, molecular dynamics simulations, Lipinski's rule of five analysis, and ADMET predictions for lead compound evaluation.
• Identified 10 compounds with optimal docking scores and 11 compounds exhibiting strong drug-likeness features.

Main Results:

• Ten novel sulfathiazole derivatives demonstrated promising docking scores against MRSA and MDR-TB receptors.
• Molecular dynamics simulations provided insights into protein stability and ligand-receptor interactions.
• Eleven compounds met Lipinski's guidelines and ADMET predictions, indicating favorable drug-like properties.

Conclusions:

• The identified sulfathiazole derivatives represent potential new therapeutic leads for developing treatments against MRSA and MDR-TB infections.
• This in silico approach effectively identified promising drug candidates for further experimental validation.
• Further research is warranted to explore the efficacy and safety of these compounds in preclinical and clinical settings.