Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Esc...

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Autores principales: Coba-Males, Manuel Alejandro, Lavecchia, Martín José, Alcívar-León, Christian David, Santamaría-Aguirre, Javier
Formato: Articulo
Lenguaje:Inglés
Publicado: 2023
Materias:
Química
molecular docking
fluoroquinolones
DNA gyrase
bacterial resistance
molecular dynamics simulations
in silico drug discovery
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/160003
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-160003
record_format dspace
spelling I19-R120-10915-1600032023-11-10T20:07:49Z http://sedici.unlp.edu.ar/handle/10915/160003 Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery Coba-Males, Manuel Alejandro Lavecchia, Martín José Alcívar-León, Christian David Santamaría-Aguirre, Javier 2023 2023-11-10T12:24:04Z en Química molecular docking fluoroquinolones DNA gyrase bacterial resistance molecular dynamics simulations in silico drug discovery Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by theWorld Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutanttype (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs. Centro de Química Inorgánica Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
molecular docking
fluoroquinolones
DNA gyrase
bacterial resistance
molecular dynamics simulations
in silico drug discovery
spellingShingle Química
molecular docking
fluoroquinolones
DNA gyrase
bacterial resistance
molecular dynamics simulations
in silico drug discovery
Coba-Males, Manuel Alejandro
Lavecchia, Martín José
Alcívar-León, Christian David
Santamaría-Aguirre, Javier
Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
topic_facet Química
molecular docking
fluoroquinolones
DNA gyrase
bacterial resistance
molecular dynamics simulations
in silico drug discovery
description Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by theWorld Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutanttype (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.
format Articulo
Articulo
author Coba-Males, Manuel Alejandro
Lavecchia, Martín José
Alcívar-León, Christian David
Santamaría-Aguirre, Javier
author_facet Coba-Males, Manuel Alejandro
Lavecchia, Martín José
Alcívar-León, Christian David
Santamaría-Aguirre, Javier
author_sort Coba-Males, Manuel Alejandro
title Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
title_short Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
title_full Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
title_fullStr Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
title_full_unstemmed Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery
title_sort novel fluoroquinolones with possible antibacterial activity in gram-negative resistant pathogens: in silico drug discovery
publishDate 2023
url http://sedici.unlp.edu.ar/handle/10915/160003
work_keys_str_mv AT cobamalesmanuelalejandro novelfluoroquinoloneswithpossibleantibacterialactivityingramnegativeresistantpathogensinsilicodrugdiscovery
AT lavecchiamartinjose novelfluoroquinoloneswithpossibleantibacterialactivityingramnegativeresistantpathogensinsilicodrugdiscovery
AT alcivarleonchristiandavid novelfluoroquinoloneswithpossibleantibacterialactivityingramnegativeresistantpathogensinsilicodrugdiscovery
AT santamariaaguirrejavier novelfluoroquinoloneswithpossibleantibacterialactivityingramnegativeresistantpathogensinsilicodrugdiscovery
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