Antonio Zandona (Avtor), Gabriela Lihtar (Avtor), Nikola Maraković (Avtor), Katarina Miš (Avtor), Valentina Bušić (Avtor), Dajana Gašo-Sokač (Avtor), Sergej Pirkmajer (Avtor), Maja Katalinić (Avtor)

Povzetek

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 [micro]M for AChE and 8 [micro]M 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.

Ključne besede

Alzheimerjeva bolezen;nikotinamid;citotoksičnost;Alzheimer's disease;nicotinamide;cytotoxicity;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL MF - Medicinska fakulteta
UDK: 616-092
COBISS: 34885635 Povezava se bo odprla v novem oknu
ISSN: 1422-0067
Št. ogledov: 143
Št. prenosov: 48
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Alzheimerjeva bolezen;nikotinamid;citotoksičnost;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-19
Letnik: ǂVol. ǂ21
Zvezek: ǂiss. ǂ21
Čas izdaje: 2020
DOI: 10.3390/ijms21218088
ID: 14363900