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Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases

1
Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10001 Zagreb, Croatia
2
Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, SLO-1001 Ljubljana, Slovenia
3
Faculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Kuhačeva 20, HR-31000 Osijek, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8088; https://doi.org/10.3390/ijms21218088
Received: 22 October 2020 / Accepted: 27 October 2020 / Published: 29 October 2020
(This article belongs to the Section Molecular Neurobiology)
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 Ki 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. View Full-Text
Keywords: AChE; BChE; neurodegenerative; Alzheimer’s; nicotinamide; cytotoxicity AChE; BChE; neurodegenerative; Alzheimer’s; nicotinamide; cytotoxicity
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MDPI and ACS Style

Zandona, A.; Lihtar, G.; Maraković, N.; Miš, K.; Bušić, V.; Gašo-Sokač, D.; Pirkmajer, S.; Katalinić, M. Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases. Int. J. Mol. Sci. 2020, 21, 8088. https://doi.org/10.3390/ijms21218088

AMA Style

Zandona A, Lihtar G, Maraković N, Miš K, Bušić V, Gašo-Sokač D, Pirkmajer S, Katalinić M. Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases. International Journal of Molecular Sciences. 2020; 21(21):8088. https://doi.org/10.3390/ijms21218088

Chicago/Turabian Style

Zandona, Antonio, Gabriela Lihtar, Nikola Maraković, Katarina Miš, Valentina Bušić, Dajana Gašo-Sokač, Sergej Pirkmajer, and Maja Katalinić. 2020. "Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases" International Journal of Molecular Sciences 21, no. 21: 8088. https://doi.org/10.3390/ijms21218088

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