20.500.12556/RUL-136941 Inhibition of MurA enzyme from Escherichia coli and Staphylococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs 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 IC$_{50}$ 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. dehydroabietane derivatives diterpenes MurA inhibitors MurF inhibitors Staphylococcus aureus MurA Escherichia coli MurA derivati dehidroabietana diterpeni zaviralci MurA zaviralci MurF bakterijske celice protibakterijsko delovanje odporni sevi antibiotiki true false true Angleški jezik Slovenski jezik Članek v reviji 2022-05-25 11:30:45 2022-05-25 11:30:50 2022-09-15 04:14:28 0000-00-00 00:00:00 2021 0 0 15 str. iss. 12, art. 1535 Vol. 10 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 543.645.7:615.3 2079-6382 10.3390/antibiotics10121535 98673411 antibiotics-10-01535.pdf antibiotics-10-01535.pdf 1 6114EBDD4722452FA78F6E2087879C32 962d83806f20bbc2366d42f099b90b9594827dddcd493580890ab694d26cffa9 6c6becbe-dc0d-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156762 https://www.mdpi.com/2079-6382/10/12/1535 1 3c25b506-dc0d-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156761 Fakulteta za farmacijo 0 0 0