Tjaša Mazej (Avtor), Damijan Knez (Avtor), Anže Meden (Avtor), Stanislav Gobec (Avtor), Matej Sova (Avtor)

Povzetek

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer's disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13-15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC50 of 4.3 [micro]M) and hBChE (IC50 of 8.5 [micro]M). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs.

Ključne besede

Alzheimer's disease;butyrylcholinesterase;monoamine oxidase B;inhibitors;multi-target-directed ligands;multifunctional ligands;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.4:54:616.894
COBISS: 69610499 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 150
Št. prenosov: 62
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: butirilholinesteraze;zaviralci;monoamin oksidaza B;večfunkcijski ligandi;tarčni ligandi;Alzheimerjeva bolezen;Farmacevtska kemija;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-17
Letnik: ǂVol. ǂ26
Zvezek: ǂiss. ǂ14
Čas izdaje: 2021
DOI: 10.3390/molecules26144118
ID: 14808630