20.500.12556/RUL-135919 Načrtovanje, sinteza in vrednotenje novih N-benzilpiperidinov kot zaviralcev holin-esteraz Design, synthesis and evaluation of novel N-benzylpiperidines as cholinesterase inhibitors Encim butirilholin-esteraza (BChE) postaja vse bolj pomembna tarča za lajšanje simptomov Alzheimerjeve bolezni. S selektivnim zaviranjem BChE lahko pomembno zvišamo koncentracijo acetilholina v možganih in tako vplivamo na potek bolezni. Na podlagi kemijske strukture spojine 2, ki je prvi nekovalentni selektivni zaviralec BChE s farmakološkim delovanjem in vivo, smo načrtovali in sintetizirali deset novih spojin z namenom poglobitve razumevanja odnosa med kemijsko strukturo in biološko učinkovitostjo. Sledilo je in vitro določanje jakosti zaviranja s pomočjo Ellmanove metode. Osem od desetih sintetiziranih spojin je bilo in vitro aktivnih, najmočnejši zaviralec BChE pa je bila spojina 10 (IC50 = 0,21 μM). V magistrski nalogi smo tako ugotovili, da je naftalen ključen za močnejše zaviranje BChE in obenem poglobili znanje o odnosu med strukturo in delovanjem selektivnih zaviralcev BChE. Butyrylcholinesterase (BChE) is becoming an increasingly important drug target for alleviating the symptoms of Alzheimer's disease. Selective inhibition of BChE can successfully increase levels of acetylcholine in central nervous system and consequently improve the course of the disease. Based on the chemical structure of the compound 2, which is the first noncovalent selective BChE inhibitor with in vivo activity, we designed and synthesized ten new compounds to better understand the structure-activity relationship. Inhibitory potency was determined in vitro with the use of the method of Ellman. Eight out of ten synthesized compounds showed in vitro inhibitory activity against BChE. The most potent BChE inhibitor is compound 10 (IC50 = 0,21 μM). We determined that the naphthalene of compound 2 is essential for potent inhibition of BChE. At the same time, we were able to deepen the knowledge and further expand the structure-activity relationship of N-benzylpiperidines as selective BChE inhibitors. butirilholin-esteraza zaviralci butirilholin-esteraze Alzheimerjeva bolezen N-benzilpiperidini butyrylcholinesterase butryrylcholinesterase inhibitors Alzheimer's disease N-benzylpiperidines true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2022-04-01 08:45:21 2022-04-01 08:45:24 2022-09-15 04:12:47 0000-00-00 00:00:00 2022 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 86909 7393.pdf 7393.pdf 1 6FD8EB5A2D969D582BB6170609E312E0 7636390779ab01bb959ec4e2efed7b3948c3b28013606743fe317f8fdf9aea60 48cf118b-b187-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155229 Fakulteta za farmacijo 0 0 0