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

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.
Hany M Abd El-Lateef 1 2,  Ayman Abo Elmaaty 3,  Lina M A Abdel Ghany 4,  Mohamed S Abdel-Aziz 5,  Islam Zaki 6,  Noha Ryad 7
Affiliations

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.
PMID: 37251193 DOI: 10.1021/acsomega.3c01156
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.

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