Inhibition of MurA Enzyme from Escherichia coli and Staphylococcus aureus by Diterpenes from Lepechinia meyenii and Their Synthetic Analogs
| Autor: | Macarena Funes Chabán, Martina Hrast, Rok Frlan, Dafni G. Graikioti, Constantinos M. Athanassopoulos, María Cecilia Carpinella |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
MurA and MurF inhibitors RM1-950 Biochemistry Microbiology MurA inhibitors bakterijske celice protibakterijsko delovanje Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Escherichia coli MurA odporni sevi udc:543.645.7:615.3 zaviralci MurF dehydroabietane derivatives diterpenes derivati dehidroabietana zaviralci MurA Infectious Diseases Staphylococcus aureus MurA diterpeni MurF inhibitors Therapeutics. Pharmacology antibiotiki |
| Zdroj: | Antibiotics, Vol 10, Iss 1535, p 1535 (2021) Antibiotics, vol. 10, no. 12, 1535, 2021. Antibiotics; Volume 10; Issue 12; Pages: 1535 |
| ISSN: | 2079-6382 |
| Popis: | Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validated as targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenes and synthetic analogs derived therefrom were investigated for their inhibitory properties on these enzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effective for inhibiting MurA from both bacteria, with IC50 values ranging from 1.1 to 25.1 µM. To further mechanistically investigate the nature of binding and to explain the activity, these compounds were docked into the active site of MurA from E. coli. The aromatic ring of the active compounds showed a T-shaped π–π interaction with the phenyl ring of Phe328, and at least one hydrogen bond was formed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establish new chemical scaffolds for the development of novel entities targeting MurA as potential antibiotics to combat the threat of pathogenic bacteria, particularly resistant strains. |
| Databáze: | OpenAIRE |
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