Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives via 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

doi:10.1021/acsomega.3c01156

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

ACS Omega. 2023 May 11;8(20):17948-17965. doi: 10.1021/acsomega.3c01156. eCollection 2023 May 23.

Authors

Hany M Abd El-Lateef^{1

2}, Ayman Abo Elmaaty³, Lina M A Abdel Ghany⁴, Mohamed S Abdel-Aziz⁵, Islam Zaki⁶, Noha Ryad⁷

Affiliations

¹ Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt.
³ Medicinal Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
⁴ Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 3236101, Egypt.
⁵ Microbial Chemistry Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, Egypt.
⁶ Pharmaceutical Organic Chemistry Department, Faculty of pharmacy, Port Said University, Port Said 42526, Egypt.
⁷ Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, P.O. Box 77, Giza 3236101, Egypt.

Abstract

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 IC₅₀ values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC₅₀ 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.