Ethylenic conjugated coumarin thiazolidinediones as new efficient antimicrobial modulators against clinical methicillin-resistant Staphylococcus aureus
| Autor: | Narsaiah Battini, Shuo Li, Yan–Fei Sui, Peng–Li Zhang, Chun–Fang Hu, Cheng He Zhou, Rong Xia Geng, Jing Lv, Mohammad Fawad Ansari |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests Drug resistance Conjugated system medicine.disease_cause 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Coumarins Drug Discovery medicine Potency Molecular Biology Norfloxacin Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Ethylenes Antimicrobial Coumarin Methicillin-resistant Staphylococcus aureus Combinatorial chemistry Anti-Bacterial Agents 0104 chemical sciences 010404 medicinal & biomolecular chemistry Thiazolidinediones DNA medicine.drug |
| Zdroj: | Bioorganic Chemistry. 94:103434 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2019.103434 |
| Popis: | In an effort for the development of novel antimicrobial agents, ethylenic conjugated coumarin thiazolidinediones as potential multi-targeting new antimicrobial compounds were synthesized through convenient procedures from commercially available resorcinol and were evaluated for their antimicrobial potency. Bioactive evaluation revealed that some of the prepared compounds showed strong antimicrobial activities towards the tested microorganisms including clinically drug-resistant strains. Especially, propargyl derivative 12b exhibited effective anti-MRSA potency with MIC value of 0.006 μmol/mL, which was highly advantageous over clinical antibacterial drug norfloxacin. Compound 12b showed rapid killing effect, low toxicity against hepatocyte LO2 cell line, and no obvious drug resistance development against MRSA. Preliminary exploration of action mechanism manifested that molecule 12b acted upon MRSA through forming stable supramolecular complex with bacterial DNA which might impede DNA replication. Molecular docking showed that compound 12b could bind with DNA-gyrase through hydrogen bonds. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect