N Ramalakshmi 1 , S R Chitra 1 , P Manimegalai 1 , S Arunkumar 2 Show Affiliations »
Abstract
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: 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: 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: 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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: 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: 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: 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Keywords:
DNA gyrase; E. coli strains; MIC results; coumarin derivatives; evaluation of novel 4-hydroxy; toxicity parameters.
Mesh： See more »
Substances： See more »
Year: 2021
PMID： 32003699 DOI： 10.2174/1573409916666200131142619
Source DB: PubMed Journal: Curr Comput Aided Drug Des ISSN： 1573-4099 Impact factor: 1.606