Affiliation:
1. Department of Chemistry Acharya Nagarjuna University Guntur Andhra Pradesh-522004 India
2. Chemical Research Department APL Research Center-II Aurobindo Pharma Ltd. Sangareddy Telangana-502329 India
3. Center for Chemical Sciences and Technology Institute of Science and Technology Jawaharlal Nehru Technological University Hyderabad Kukatpally, Hyderabad Telangana-500085 India
4. Department of Chemistry, GITAM Institute of Science GITAM (Deemed to be University) Gandhi Nagar, Rushikonda, Visakhapatnam Andhra Pradesh-530045 India
5. Department of Chemistry Institute of Aeronautical Engineering Dundigal, Hyderabad Telangana-500043 India
6. Advanced Center of Research in High Energy Materials University of Hyderabad Hyderabad Telangana-500046 India
Abstract
AbstractOur current work is aimed at synthesizing novel substituted 1,2,4‐triazolyl‐fluoroquinolone analogs and study of their biological activity to find active promising molecules. The structural elucidation of the products was demonstrated by a variety of spectroscopic methods such as IR, 1H‐NMR, 13C‐NMR, mass and elemental analysis. The newly synthesized 1,2,4‐triazole derivatives were tested in vitro for their ability to inhibit the growth of seven different microbes including S. epidermidis, S. pneumoniae, S. aureus, B. subtilis, K. pneumoniae, E. coli, and P. aeruginosa. Five FQ derivatives 5d, 5e, 5h, 5j, and 5b have demonstrated good antibacterial activity against S. pneumoniae with MICs ranging from 2.5–22.0 μg/mL, while 5c, 5g reported comparable activity against P. aeruginosa with respect to the standard drugs moxifloxacin and ciprofloxacin. The possible mechanism of antibacterial activity of fluoroquinolones was investigated via molecular docking by using DNA gyrase of S. pneumoniae (3RAE). The pefloxacin derivatives also tended a good antibacterial ability based on the results of the molecular docking, ligand 5h with good binding affinity (−9.92 Kcal/mol) and binding site interactions via ValA:86, SerA:79, TyrA:82, MetA:116, AspA:78, AlaA:63, ArgA:117, ProA:112, ProA:113, AlaA:115, AlaA:114. These scaffolds were further evaluated for their ADMET and physicochemical properties by using SwissADME, ADMETlab2.0 web server as a good oral bioavailability.
Subject
Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering