Norfloxacin Derivatives as DNA Gyrase and Urease Inhibitors: Synthesis, Biological Evaluation and Molecular Docking

Abstract

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn’s disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (¹H NMR, Fourier transform IR, ¹³C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC₅₀ of 0.15 ± 0.24 and 1.14 ± 0.11 μM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.

Graphical abstract

Keywords::

• bactericidal
• DPPH scavenging
• enzyme inhibition
• esters

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/fmc-2023-0225

Author contributions

All authors contributed to the study’s conception and design. Writing the original draft, reviewing, performing the experiments, collecting results and all other study data were performed by B Awan. The ideas, formulation of overarching research aims, design of methodology and creation of models were presented by MA Khan. The management of activities was performed by I Ahmad. The maintenance of research data and coordination responsibility for the research activity planning and execution was done by A Masood. A Raza checked the verification and reproducibility of the results. S Khaliq applied statistical techniques to analyze study data. F Ullah contributed ton programming and software development. J Ahmed provided study materials and reagents. MR Khan contributed to the compilation of results. All authors have read and agreed to the published version of the manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Data sharing statement

Data can be provided on demand from corresponding author.