Comprehensive Computational Screening of 2-(2-(5-phenyl-1H-tetrazol-1-yl)ethyl)-1,2-thiazetidine 1,1-dioxide Derivatives as Potential Agents for Next-Generation Antibiotic Combating Drug-Resistant Community-Acquired Bacterial Pneumonia (CABP)
نویسندگان
1 Department of Pharmaceutical Chemistry, P. Rami Reddy Memorial College of Pharmacy, Kadapa, Andhra Pradesh, India
2 Department of Pharmaceutical Analysis, Joginpally B. R. Pharmacy college, yenkapally, Moinabad 500075, Telangana, India
3 Department of Pharmaceutical Chemistry, Pt Rajendra Prasad Smarak College of Pharmacy, Kajri-Niranjanpur, Puranpur, Pilibhit, Uttar Pradesh 262122, India
4 Department of Pharmaceutics, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, India
5 Department of Pharmaceutical Chemistry, Government College of Pharmacy, Osmanpura, Chhatrapati Sambhajinagar 431005, Maharashtra, India
6 Pharmacological and Diagnostic Research Centre (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
7 Department of Pharmacy, Teerthanker Mahaveer college of pharmacy, TMU, Moradabad 244001 Uttar Pradesh, India
8 Department of Pharmaceutical Chemistry, Apollo Institute of Pharmaceutical Sciences, The Apollo University, The Apollo Knowledge City, Saketa, Chittoor 517127, Andhra Pradesh, India
doi
10.48309/ajca.2025.530183.1864چکیده
This study offers molecular docking and extensive in silico ADMET evaluation of 20 novel 2-(2-(5-phenyl-1H-tetrazol-1-yl)ethyl)-1,2-thiazetidine 1,1-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 (CC2, CC4, CC9, CC12, CC13, CC14, and CC15) had enhanced binding affinities relative to the natural ligand, with docking scores between -8.1 and -9.0 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 CC1, CC2, CC16, CC17, and CC18 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-2 and MDCK models, significant P-glycoprotein interactions, and heightened forecasts for human intestinal absorption. They demonstrated suitable distribution patterns, manageable cytochrome P450 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.
