RESUMEN
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.
Asunto(s)
Antibacterianos/síntesis química , Simulación por Computador , Cumarinas/síntesis química , Diseño de Fármacos/métodos , Simulación del Acoplamiento Molecular/métodos , Antibacterianos/farmacología , Cumarinas/farmacología , Evaluación Preclínica de Medicamentos/métodos , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Humanos , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
The newly emerging infectious organisms, the global crisis in antibiotic resistance, and the threat of bioterrorism create an urgent need to discover novel antimicrobial agents. In order to develop novel antimicrobial agents, the mechanism of infectious disease must be better understood. DNA Gyrase is a bacterial enzyme that plays an important role in the replication of DNA and transcription process. It is not present in higher eukaryotes making it a perfect target for developing new antibacterial agents. This review describes the role of DNA gyrase inhibitors in preventing various diseases. In this review, we outline the synthesis and pharmacological action of various novel DNA gyrase inhibitors. DNA gyrase inhibitors were used to treat tuberculosis, bacterial, fungal infections and malaria. DNA gyrase inhibitors mainly act by preventing the supercoiling of DNA strands..