Synthesis, Characterization, Molecular Docking and Evaluation of Fluoroquinolone Derivatives as Dual-Targeting Agents

Authors

• Murtadha F. Abdullah, Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry, College of Pharmacy, University of Basrah, Basrah, IraqFollow
• Raheem J Mohaisen, Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry, College of Pharmacy, University of Basrah, Basrah, Iraq

Article Type

Article

Abstract

Background: The rapid emergence of antimicrobial resistance and persistence of urease-associated bacterial infections underscores the urgent need for alternative therapeutic strategies. Urease is a key virulence factor that plays a critical role in pathogenesis of several pathogenic bacteria by promoting colonization and survival in acidic environment. Objective: In this context, this study aimed to develop some fluoroquinolone derivatives hybridized with urease targeting small molecule and evaluating their potential as dual urease inhibiting antibacterial agents. We hypothesized that hybridization of fluoroquinolone core with urease targeting small molecule using a cleavable linker could potentially disarm the microbe's key virulence factor ``urease enzyme'' while fluoroquinolone's core provides the antibacterial effect. Method: The derivatives were synthesized through Steglich reaction using standard protocols and previously described procedures. Characterization of target compounds was done using Fourier Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) and Mass Spectrometry. The synthesized compounds were evaluated for urease inhibition activity as well as antibacterial activity using agar well diffusion method. Results: The results indicates that compounds (M1-3) showed promising urease inhibition activity with compound M3 being the most potent with an IC₅₀ of (34.69μg/ml). Antibacterial activity revealed that compound M1 had higher potency against gram-positive bacteria (S. aureus and S. mutans) while M3 was the most potent against gram-negative (P. aeruginosa). Conclusion: Biological evaluation of synthesized fluoroquinolone derivatives revealed that compound M1-3 showed promising biological activity, indicating potential as dual targeting agents and warranting further investigations to optimize and develop in-vivo applications.

Keywords

Fluoroquinolones, Hybridization, Dual-targeting agents, Antimicrobial resistance, Urease inhibition

Recommended Citation

Abdullah, Murtadha F. and Mohaisen, Raheem J (2026) "Synthesis, Characterization, Molecular Docking and Evaluation of Fluoroquinolone Derivatives as Dual-Targeting Agents," Muthanna Medical Journal: Vol. 13: Iss. 2, Article 10.
Available at: https://muthmj.mu.edu.iq/journal/vol13/iss2/10

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This work is licensed under a Creative Commons Attribution 4.0 International License.