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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Halyna Hryhoriv, Illia Mariutsa, Sergiy M. Kovalenko, Lyudmila Sidorenko, Lina Perekhoda, Nataliia Filimonova, Olga Geyderikh, Victoriya Georgiyants
Formato:	article
Lenguaje:	EN
Publicado:	PC Technology Center 2021
Materias:	fluoroquinolones ciprofloxacin norfloxacin synthesis antibiotic resistance molecular docking antibacterial activity Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/cc95543aeaf74377929ba12b835fd7e4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cc95543aeaf74377929ba12b835fd7e4
record_format	dspace
spelling	oai:doaj.org-article:cc95543aeaf74377929ba12b835fd7e42021-11-04T14:22:47ZStructural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria2519-48442519-485210.15587/2519-4852.2021.242997https://doaj.org/article/cc95543aeaf74377929ba12b835fd7e42021-10-01T00:00:00Zhttp://journals.uran.ua/sr_pharm/article/view/242997https://doaj.org/toc/2519-4844https://doaj.org/toc/2519-4852The 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 resistanceHalyna HryhorivIllia MariutsaSergiy M. KovalenkoLyudmila SidorenkoLina PerekhodaNataliia FilimonovaOlga GeyderikhVictoriya GeorgiyantsPC Technology Centerarticlefluoroquinolonesciprofloxacinnorfloxacinsynthesisantibiotic resistancemolecular dockingantibacterial activityPharmacy and materia medicaRS1-441ENScienceRise: Pharmaceutical Science, Iss 5(33), Pp 4-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fluoroquinolones ciprofloxacin norfloxacin synthesis antibiotic resistance molecular docking antibacterial activity Pharmacy and materia medica RS1-441
spellingShingle	fluoroquinolones ciprofloxacin norfloxacin synthesis antibiotic resistance molecular docking antibacterial activity Pharmacy and materia medica RS1-441 Halyna Hryhoriv Illia Mariutsa Sergiy M. Kovalenko Lyudmila Sidorenko Lina Perekhoda Nataliia Filimonova Olga Geyderikh Victoriya Georgiyants Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
description	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
format	article
author	Halyna Hryhoriv Illia Mariutsa Sergiy M. Kovalenko Lyudmila Sidorenko Lina Perekhoda Nataliia Filimonova Olga Geyderikh Victoriya Georgiyants
author_facet	Halyna Hryhoriv Illia Mariutsa Sergiy M. Kovalenko Lyudmila Sidorenko Lina Perekhoda Nataliia Filimonova Olga Geyderikh Victoriya Georgiyants
author_sort	Halyna Hryhoriv
title	Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
title_short	Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
title_full	Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
title_fullStr	Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
title_full_unstemmed	Structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
title_sort	structural modification of ciprofloxacin and norfloxacin for searching new antibiotics to combat drug-resistant bacteria
publisher	PC Technology Center
publishDate	2021
url	https://doaj.org/article/cc95543aeaf74377929ba12b835fd7e4
work_keys_str_mv	AT halynahryhoriv structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT illiamariutsa structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT sergiymkovalenko structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT lyudmilasidorenko structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT linaperekhoda structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT nataliiafilimonova structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT olgageyderikh structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria AT victoriyageorgiyants structuralmodificationofciprofloxacinandnorfloxacinforsearchingnewantibioticstocombatdrugresistantbacteria
_version_	1718444868594827264

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

Ejemplares similares