New Fluoroquinolone-1,2,4-triazoles as Potent Antibacterial Agents: Design,Synthesis, Docking Studies and in Silico ADME Profiles |
| |
Authors: | Venkateswara Rao Gollapalli Hari Babu Bollikolla Tejeswara Rao Allaka Pandu Ranga Rao Vaddi Sravanthi Basireddy Mutyalanaidu Ganivada Santhosh Reddy Pindi |
| |
Affiliation: | 1. Department of Chemistry, Acharya Nagarjuna University, Guntur, Andhra Pradesh-522004 India;2. Center for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, Telangana-500085 India;3. Chemical Research Department, APL Research Center-II, Aurobindo Pharma Ltd., Sangareddy, Telangana-502329 India;4. Department of Chemistry, GITAM Institute of Science, GITAM (Deemed to be University), Gandhi Nagar, Rushikonda, Visakhapatnam, Andhra Pradesh-530045 India Department of Chemistry, Institute of Aeronautical Engineering, Dundigal, Hyderabad, Telangana-500043 India;5. Advanced Center of Research in High Energy Materials, University of Hyderabad, Hyderabad, Telangana-500046 India |
| |
Abstract: | Our 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. |
| |
Keywords: | fluoroquinolones 1,2,4-triazoles antimicrobial activity molecular modeling 3RAE protein ADMETlab2.0 |
|
|