Macarena Funes Chabán (Author), Martina Hrast (Author), Rok Frlan (Author), Dafni G. Graikioti (Author), Constantinos M.  Athanassopoulos (Author), María Cecilia Carpinella (Author)

Abstract

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.

Keywords

dehydroabietane derivatives;diterpenes;MurA inhibitors;MurF inhibitors;Staphylococcus aureus MurA;Escherichia coli MurA;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 543.645.7:615.3
COBISS: 98673411 Link will open in a new window
ISSN: 2079-6382
Views: 125
Downloads: 26
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Other data

Secondary language: Slovenian
Secondary keywords: derivati dehidroabietana;diterpeni;zaviralci MurA;zaviralci MurF;bakterijske celice;protibakterijsko delovanje;odporni sevi;Antibiotiki;
Type (COBISS): Article
Pages: str. 1-15
Volume: ǂVol. ǂ10
Issue: ǂiss. ǂ12
Chronology: 2021
DOI: 10.3390/antibiotics10121535
ID: 15417507