20.500.12556/RUL-141341 Stereoselective activity of 1-propargyl-4-styrylpiperidine-like analogues that can discriminate between monoamine oxidase isoforms A and B The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis- and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms. binding energy ethyl groups inhibition inhibitors molecular structure razvoj zdravil toksikologija zdravil monoamin oksidaze true false true Angleški jezik Angleški jezik Članek v reviji 2022-09-28 13:38:49 2022-09-28 13:38:52 2022-09-29 04:03:53 0000-00-00 00:00:00 2020 0 0 Str. 1361-1387 iss. 3 Vol. 63 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.35:615.015:615.9 0022-2623 10.1021/acs.jmedchem.9b01886 4872561 acs.jmedchem.9b01886.pdf acs.jmedchem.9b01886.pdf 1 975680808ED074A0B762EE2EE2A485DC 9a146a2c9b4b3f586452bc50a1f00d317916919e5e692f73df5116ce87e2f0ae 10b81670-3f23-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162376 https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01886 1 1fb0dfa0-3f22-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162375 Fakulteta za farmacijo 0 0 0