Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives <i>via</i> Molecular Hybridization as Novel Microbial DNA-Gyrase Inhibitors
Hany M. Abd El‐Lateef, Ayman Abo Elmaaty, Lina M. A. Abdel Ghany, Mohamed S. Abdel‐Aziz, Islam Zaki, Noha Ryad
Abstract
High Resolution Image Download MS PowerPoint Slide Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives ( 5 – 14 ) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. The investigated compounds displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacin as a reference control. Obviously, compounds 6b and 10 unveiled IC 50 values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC 50 value of 3.80 μM. Furthermore, a significant docking binding score was encountered by compound 6b (−7.73 kcal/mol), surpassing ciprofloxacin (−7.29 kcal/mol). Additionally, both compounds 6b and 10 revealed high GIT absorption without passing the blood brain barrier. Finally, the conducted structure−activity relationship study assured the usefulness of the hydrazine moiety as a molecular hybrid for activity either in cyclic or opened form.