20.500.12556/RUL-134685 Vitamin B3-based biologically active compounds as inhibitors of human cholinesterases We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds reversibly inhibited both enzymes in the micromolar range pointing to the preference of AChE over BChE for binding the tested derivatives. Molecular docking studies revealed the importance of interactions with AChE active site residues Tyr337 and Tyr124, which dictated most of the observed differences. The most potent inhibitor of both enzymes with K$_i$ of 4 µM for AChE and 8 µM for BChE was the nicotinamide derivative 1-(4′-phenylphenacyl)-3-carbamoylpyridinium bromide. Such a result places it within the range of several currently studied novel cholinesterase inhibitors. Cytotoxicity profiling did not classify this compound as highly toxic, but the induced effects on cells should not be neglected in any future detailed studies and when considering this scaffold for drug development. Alzheimer's disease nicotinamide cytotoxicity AChE BChE neurodegenerative Alzheimerjeva bolezen nikotinamid citotoksičnost true false true Angleški jezik Slovenski jezik Članek v reviji 2022-01-26 09:25:12 2022-01-26 09:25:16 2022-09-13 03:56:32 0000-00-00 00:00:00 2020 0 0 19 str. iss. 21, art. 8088 Vol. 21 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 1422-0067 10.3390/ijms21218088 34885635 RAZ_Zandona_Antonio_2020.pdf RAZ_Zandona_Antonio_2020.pdf 1 4179CAA495D3F8BEE3BA4A6974FDBFD5 8ebaa6aa2365c9dade7f5fa6e552875519c851087a572067dec80aefb669ea00 e3de40ac-7e82-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153252 https://www.mdpi.com/1422-0067/21/21/8088 0 4a182d5a-7e81-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153251 Medicinska fakulteta 0 0 0