Docking study of novel designed indazole derivatives against topoisomerase-II DNA gyrase enzyme for antibacterial screening

Abstract

Aim of the study was designed for the design of novel indazole derivatives and evaluation of their docking against topoisomerase-II DNA gyrase enzyme for the antibacterial screening. Different novel substituted indazol-3-yl benzenesulfonamide derivatives were designed for the synthesis from o-chlorobenzonitrile and phenyl hydrazine reaction and further, with benzene sulphonyl chloride reaction. These were evaluated for their docking targeting topoisomerase-II DNA gyrase enzyme for the antibacterial screening. A range of binding affinity (-12.2 to -9.6 kcal/mol) was observed. Compound, 4-chloro-N-(1-phenyl-1H-indazol-3-yl)benzenesulfonamide had the highest binding affinity (-12.2 kcal/mol) which is better than the standard norfloxacin (-10.7 kcal/mol). Compounds (12a, 12c, 12e and 12g) with chloro-substitution at para position of sulfonamide had higher affinity as compared to the compounds (12b, 12d, 12f and 12h) with methyl substitution. A convenient method for the synthesis of indazole derivatives has been developed. 4-chloro-N-(1-phenyl-1H-indazol-3-yl)benzenesulfonamide had shown the best binding affinity. Further, more diverse bioactive moieties may be incorporated into indazole scaffold in the near future by future researchers and a great amount of effort may be dedicated to the exploration of medicinal approaches for their preparation and evaluation of their biological activities.

Keywords

Docking / Indazole / Pyrazole / Topoisomerase-II / DNA gyrase / Antibacterial

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