Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.242997

Keywords:

fluoroquinolones, ciprofloxacin, norfloxacin, synthesis, antibiotic resistance, molecular docking, antibacterial activity

Abstract

The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives.

Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains.

The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method.

Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistance

Author Biographies

Halyna Hryhoriv, National University of Pharmacy

PhD

Department of Pharmaceutical Chemistry

Illia Mariutsa, National University of Pharmacy

Postgraduate Student

Department of Organic Chemistry

Sergiy M. Kovalenko, V. N. Karazin Kharkiv National University

Doctor of Chemical Sciences, Professor

Department of Organic Chemistry

Lyudmila Sidorenko, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmaceutical Chemistry

Lina Perekhoda, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Medicinal Chemistry

Nataliia Filimonova, National University of Pharmacy

Doctor of Medical Sciences, Professor

Department of Microbiology, Virology and Immunology

Olga Geyderikh, National University of Pharmacy

PhD, Associate Professor

Department of Microbiology, Virology and Immunology

Victoriya Georgiyants, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmaceutical Chemistry

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Published

2021-10-29

How to Cite

Hryhoriv, H., Mariutsa, I., Kovalenko, S. M., Sidorenko, L., Perekhoda, L., Filimonova, N., Geyderikh, O., & Georgiyants, V. (2021). Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria. ScienceRise: Pharmaceutical Science, (5(33), 4–11. https://doi.org/10.15587/2519-4852.2021.242997

Issue

No. 5(33) (2021)

Section

Pharmaceutical Science

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Copyright (c) 2021 Halyna Hryhoriv, Illia Mariutsa, Sergiy M. Kovalenko, Lyudmila Sidorenko, Lina Perekhoda, Nataliia Filimonova, Olga Geyderikh, Victoriya Georgiyants

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