Comprehensive Computational Screening of ۲-(۲-(۵-phenyl-۱H-tetrazol-۱-yl)ethyl)-۱,۲-thiazetidine ۱,۱-dioxide Derivatives as Potential Agents for Next-Generation Antibiotic Combating Drug-Resistant Community-Acquired Bacterial Pneumonia (CABP)

This study offers molecular docking and extensive in silico ADMET evaluation of ۲۰ novel ۲-(۲-(۵-phenyl-۱H-tetrazol-۱-yl)ethyl)-۱,۲-thiazetidine ۱,۱-dioxide derivatives as potential next-generation antibiotics for addressing drug-resistant community-acquired bacterial pneumonia (CABP). Initially selected through molecular docking for their strong binding affinities, promising derivatives were subjected to ADMET profiling to evaluate their drug-likeness and pharmacokinetic suitability. Molecular docking analyses indicated that numerous compounds (CC۲, CC۴, CC۹, CC۱۲, CC۱۳, CC۱۴, and CC۱۵) had enhanced binding affinities relative to the natural ligand, with docking scores between -۸.۱ and -۹.۰ kcal/mol. These compounds demonstrated extensive hydrogen-bonding networks with other interactions such as π-sulfur, π-π stacking, and π-alkyl interactions. ADMET analysis identified CC۱, CC۲, CC۱۶, CC۱۷, and CC۱۸ as the most promising candidates, demonstrating favorable physicochemical properties, high drug-likeness scores, enhanced absorption characteristics, and acceptable toxicity profiles. These pharmaceuticals exhibit enhanced permeability in Caco-۲ and MDCK models, significant P-glycoprotein interactions, and heightened forecasts for human intestinal absorption. They demonstrated suitable distribution patterns, manageable cytochrome P۴۵۰ enzyme interactions, and low hepatotoxicity and carcinogenic risk. This extensive investigation offers a solid foundation for the further development and enhancement of these compounds as potential next-generation antibiotics to combat drug-resistant CABP.

کلیدواژه ها:

CABP ، next-generation antibiotic ، Computational investigation ، ADMET ، Molecular docking