Design, Synthesis, Antibacterial Activity and in Silico Studies of Novel Quinolone Fused with Triazine, Thiadiazole and Oxadiazole Heterocycles

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.

Graphical Abstract

Keywords:

• Quinolone; 1,2,4-triazole; 1,3,4-thiadiazole; 1,3,4-oxadiazole; antibacterial activity; molecular docking

Acknowledgements

The authors thank Schrodinger Inc. for the Schrodinger molecular modelling suite to perform the molecular docking studies. The authors are also thankful to Priyanka Desai, founder of iScribblers, for the linguistic editing of the manuscript.

Disclosure statement

The present article does not possess any human and animal trail and all the authors are not involved any type of such experiments. Over and above, authors declare that they have no conflict of interest.

Scheme 1. Synthesis for the preparation of title compounds.

Additional information

Funding

One of the authors Prof. Nisheeth C Desai is thankful to UGC for awarding BSR faculty fellowship-2019 (No. F18-1/2011 (BSR)) and financial assistant. The authors are thankful to the University Grants Commission, New Delhi, and Department of Science and Technology, New Delhi, for financial support under the NON-SAP and DST-FIST programs, respectively.