Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives via Molecular Hybridization as Novel Microbial DNA-Gyrase Inhibitors

Microbial DNA gyraseis regarded as an outstanding microbial target.Hence, 15 new quinoline derivatives (5-14) were designed and synthesized. The antimicrobial activity of theafforded compounds was pursued via in vitro approaches.The investigated compounds displayed eligible MIC values, particularlyagainst G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacinas a reference control. Obviously, compounds 6b and 10 unveiled IC50 values of 33.64 and 8.45 & mu;M,respectively. Alongside, ciprofloxacin exhibited an IC50 value of 3.80 & mu;M. Furthermore, a significant docking bindingscore was encountered by compound 6b (-7.73 kcal/mol),surpassing ciprofloxacin (-7.29 kcal/mol). Additionally, bothcompounds 6b and 10 revealed high GIT absorptionwithout passing the blood brain barrier. Finally, the conducted structure-activityrelationship study assured the usefulness of the hydrazine moietyas a molecular hybrid for activity either in cyclic or opened form.