20.500.12556/RUL-154069 Inhibition of MurA enzyme from Escherichia coli by flavonoids and their synthetic analogues MurA catalyzes the first step of peptidoglycan (PG) biosynthesis and is a validated target for the development of new antimicrobial agents. In this study, a library of 49 plant flavonoids and their synthetic derivatives were evaluated for their inhibitory properties against MurA from Escherichia coli. The compounds were tested with and without preincubation and with the addition of DTT to understand the mechanism of inhibition. Thirteen compounds were identified as reversible, time-dependent inhibitors, with inhibition levels ranging from 480 nM to 57 μM, and ampelopsin as the most potent compound. To investigate the major pharmacophore elements responsible for the activity, 2D-QSAR and docking analyzes were performed. The results showed that the catechol moiety and an additional aromatic system were the most important features contributing to the activity of the compounds. However, most of the compounds did not show antibacterial activity against E. coli and Staphylococcus aureus strains, suggesting that their inhibitory activity against MurA may not be strong enough to induce antibacterial effects. Nevertheless, our results suggest that flavonoids are a promising starting point to develop new inhibitors of MurA and show great potential for further steps in drug development. assays flavonoids inhibition inhibitors peptides proteins testi inhibicija zaviralci proteini flavonoidi bakterijska rezistenca peptidi beljakovine true false true Angleški jezik Slovenski jezik Članek v reviji 2024-01-23 09:56:55 2024-01-23 09:57:00 2024-01-31 03:50:02 0000-00-00 00:00:00 2023 0 0 Str. 33006-33016 iss. 36 Vol. 8 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.972:615.015.8 2470-1343 10.1021/acsomega.3c04813 181848835 frlan-et-al-2023-inhibition-of-mura-enzyme-from-escherichia-coli-by-flavonoids-and-their-synthetic-analogues.pdf frlan-et-al-2023-inhibition-of-mura-enzyme-from-escherichia-coli-by-flavonoids-and-their-synthetic-analogues.pdf 1 98998552153A0EBAF9C82FC38E32BABB 064c2109736bee6f8d0ef1624398a0d7552c50a2fd43e616c8af97f4c7609514 bd75eedb-bf7d-11ee-ab6c-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=180408 https://pubs.acs.org/doi/10.1021/acsomega.3c04813 1 5f1bb985-b9cd-11ee-b1f4-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=180224 Fakulteta za farmacijo 0 0 0