| Autor: |
Ivan Semenyuta, Diana Hodyna, Vasyl Kovalishyn, Bohdan Demydchuk, Maryna Kachaeva, Stepan Pilyo, Volodymyr Brovarets, Larysa Metelytsia |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Artificial Intelligence Chemistry, Vol 1, Iss 2, Pp 100024- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2949-7477 |
| DOI: |
10.1016/j.aichem.2023.100024 |
| Popis: |
Here we describe the results of QSAR analysis based on artificial neural networks, synthesis, activity evaluation and molecular docking of a number of 1,3-oxazole derivatives as anti-E. coli antibacterials. All developed QSAR models showed excellent statistics on training (with determination coefficient q2 as 0.76 ± 0.01) and test samples (with q2 as 0.78 ± 0.01). The models were successfully used to identify nine novel 5-amino-4-cyano-1,3-oxazoles with potential anti-E. coli activity. All nine 1,3-oxazoles with predicted high antibacterial potential showed different levels of anti- E. coli in vitro activity. 5-amino-4-cyano-1,3-oxazoles 1 and 3 showed the highest antibacterial activity on average from 17 to 27 mm against MDR, hemolytic MDR and ATCC 25922 E. coli colistin-resistant strains, respectively. The comparative docking analysis demonstrated a possible mechanism of the antibacterial action of the studied 1, 3-oxazoles 1 and 3 through inhibition of E. coli enoyl-ACP reductase (ENR) involved in the biosynthesis of bacterial fatty acids. The localization type is shown of 5-amino-4-cyano-1,3-oxazoles 1 and 3 into the E. coli ENR active site with estimated binding energy from − 10.1 to − 9.5 kcal/mol and hydrogen bonds formation with key amino acids similar to Triclosan. These facts confirm the validity of the hypothesis put forward about the potential antibacterial mechanism of 5-amino-4- cyano-1,3-oxazoles. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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