Design, Synthesis, Antibacterial Activity and <i>in Silico</i> Studies of Novel Quinolone Fused with Triazine, Thiadiazole and Oxadiazole Heterocycles
Nisheeth C. Desai, Kashyap R. Wadekar, Harsh K. Mehta, Unnat Pandit, Vijay M. Khedkar
Abstract
We have strategically designed and synthesized some novel quinolone fused with hybrid heterocycles 7-chloro-1-ethyl-6-fluoro-4-oxo-N'-(arylcarbonothioyl)-1,4-dihydroquinoline-3-carbohydrazides (3a–m), 7-chloro-1-ethyl-6-fluoro-3-(5-mercapto-4-aryl-4H-1,2,4-triazol-3-yl)quinolin-4-ones (4a–m), 7-chloro-1-ethyl-6-fluoro-3-(5-(arylamino)-1,3,4-thiadiazol-2-yl)quinolin-4(1H)-ones (5a–m) and 7-chloro-1-ethyl-6-fluoro-3-(5-(arylamino)-1,3,4-oxadiazol-2-yl)quinolin-4(1H)-ones (6a–m) and screened them against bacterial strains. Results of antibacterial efficacy revealed that compounds with electron-withdrawing groups like 3b, 3c, 3d, 4c, 4d, 4e, 5b, 5c and 5d showed better activity against different bacterial strains among the synthesized compounds 3a–m, 4a–m, and 5a–m while compounds having electron-donating groups like 6h, 6i, 6j and 6k displayed better activity in synthesized compounds 6a–m. Furthermore, molecular docking against microbial DNA gyrase could throw light into the plausible mechanism of action and thermodynamic interactions governing the binding of these molecules. The article provides various synthetic approaches for strategically designed different hybrid heterocycles which were further evaluated for their biological activities against bacterial strains, to offer the findings for future research and to give a path-breaking lead in designing potent compounds managing the bacterial resistance strains.