20.500.12556/RUL-152205 Mur ligase F as a new target for the flavonoids quercitrin, myricetin, and (–)-epicatechin MurC, D, E, and F are ATP-dependent ligases involved in the stepwise assembly of the tetrapeptide stem of forming peptidoglycan. As highly conserved targets found exclusively in bacterial cells, they are of significant interest for antibacterial drug discovery. In this study, we employed a computer-aided molecular design approach to identify potential inhibitors of MurF. A biochemical inhibition assay was conducted, screening twenty-four flavonoids and related compounds against MurC-F, resulting in the identification of quercitrin, myricetin, and (–)-epicatechin as MurF inhibitors with IC$_{50}$ values of 143 µM, 139 µM, and 92 µM, respectively. Notably, (–)-epicatechin demonstrated mixed type inhibition with ATP and uncompetitive inhibition with D-Ala-D-Ala dipeptide and UM3DAP substrates. Furthermore, in silico analysis using Sitemap and subsequent docking analysis using Glide revealed two plausible binding sites for (–)-epicatechin. The study also investigated the crucial structural features required for activity, with a particular focus on the substitution pattern and hydroxyl group positions, which were found to be important for the activity. The study highlights the significance of computational approaches in targeting essential enzymes involved in bacterial peptidoglycan synthesis. MurF quercitrin myricetin (–)-epicatechin antibacterial activity MurF kvercitrin miricetin (–)-epikatehin antibakterijsko delovanje farmacevtska kemija tarčna zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2023-11-10 10:53:11 2023-11-10 10:53:16 2023-11-16 03:46:09 0000-00-00 00:00:00 2023 0 0 Str. 721-733 iss. 12 Vol. 37 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.277.3 0920-654X 10.1007/s10822-023-00535-z 167509251 s10822-023-00535-z.pdf s10822-023-00535-z.pdf 1 C2BA58CEC9A0B7986D051BFBE9678CBF 10707e4f54f05604c08101f113acff8b9c3d74766ddcff3f4be399ab685f7d97 9fa15460-83b6-11ee-9a01-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177669 https://link.springer.com/article/10.1007/s10822-023-00535-z 1 f900f752-7fae-11ee-bf5f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177553 Fakulteta za farmacijo Veterinarska fakulteta 0 0 0