Design, Synthesis, Docking and Biological Evaluation of Novel 4-hydroxy Coumarin Derivatives.
DNA gyrase
E. coli strains
MIC results
coumarin derivatives
evaluation of novel 4-hydroxy
toxicity parameters.
Journal
Current computer-aided drug design
ISSN: 1875-6697
Titre abrégé: Curr Comput Aided Drug Des
Pays: United Arab Emirates
ID NLM: 101265750
Informations de publication
Date de publication:
2021
2021
Historique:
received:
26
09
2019
revised:
20
11
2019
accepted:
15
01
2020
pubmed:
1
2
2020
medline:
15
12
2021
entrez:
1
2
2020
Statut:
ppublish
Résumé
Hospital-acquired (HA) infections are caused due to E. coli, which is resistant to multiple drugs particularly to fluoroquinolone class of drugs. Urinary tract infections (UTI) affects people in the community and hospitals. 150 million people per annum are suffering from UTI worldwide. In this present study, we designed 36 novel coumarin derivatives, also we predicted pharmacokinetic and toxicity parameters. Docking studies were also carried out and all the compounds were evaluated for antibacterial activity against resistant quinolone E. coli strain ATCC 25922. It was interesting to note that the introduction of electron-withdrawing group on the aromatic ring resulted in compounds with an increased antibacterial activity, which is observed in compound 6 (with 4-nitro substitution), compound 23 (chloro) and compound 30 (chloro, nitro). From the MIC results, it was observed that compounds 6, 23 and 30 showed higher activity with 0.5μg/ml, 0. 12 μg/ml, 0.5 μg/ml respectively. Docking studies were performed with the active site of DNA gyrase (PDB ID: 4CKK). The maximum binding energy was found to be -10.7 Kcal/mol. From the study, it was found that 3 compounds were potentially active against quinolone- resistant E. coli strains. This study can further be extended for in vivo evaluation.
Sections du résumé
BACKGROUND
BACKGROUND
Hospital-acquired (HA) infections are caused due to E. coli, which is resistant to multiple drugs particularly to fluoroquinolone class of drugs. Urinary tract infections (UTI) affects people in the community and hospitals. 150 million people per annum are suffering from UTI worldwide.
METHODS
METHODS
In this present study, we designed 36 novel coumarin derivatives, also we predicted pharmacokinetic and toxicity parameters. Docking studies were also carried out and all the compounds were evaluated for antibacterial activity against resistant quinolone E. coli strain ATCC 25922. It was interesting to note that the introduction of electron-withdrawing group on the aromatic ring resulted in compounds with an increased antibacterial activity, which is observed in compound 6 (with 4-nitro substitution), compound 23 (chloro) and compound 30 (chloro, nitro).
RESULTS
RESULTS
From the MIC results, it was observed that compounds 6, 23 and 30 showed higher activity with 0.5μg/ml, 0. 12 μg/ml, 0.5 μg/ml respectively. Docking studies were performed with the active site of DNA gyrase (PDB ID: 4CKK). The maximum binding energy was found to be -10.7 Kcal/mol.
CONCLUSION
CONCLUSIONS
From the study, it was found that 3 compounds were potentially active against quinolone- resistant E. coli strains. This study can further be extended for in vivo evaluation.
Identifiants
pubmed: 32003699
pii: CAD-EPUB-104146
doi: 10.2174/1573409916666200131142619
doi:
Substances chimiques
Anti-Bacterial Agents
0
Coumarins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
201-213Informations de copyright
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