Michalina Hebda (Avtor), Marek Bajda (Avtor), Anna Więckowska (Avtor), Natalia Szałaj (Avtor), Anna Pasieka (Avtor), Dawid Panek (Avtor), Justyna Godyń (Avtor), Tomasz Wichur (Avtor), Damijan Knez (Avtor), Stanislav Gobec (Avtor), Barbara Malawska (Avtor)

Povzetek

Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer's disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM). Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE) (EeAChE IC50 = 0.76 microM, EqBuChE IC50 = 0.618 microM), and it inhibits amyloid beta aggregation (35.8% at 10 microM). Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB) was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer's agents.

Ključne besede

tarčna zdravila;razvoj zdravil;zaviralci acetilholinesteraze;molekularno modeliranje;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.2:616.894
COBISS: 4051313 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 191
Št. prenosov: 61
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;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-24
Letnik: ǂVol. ǂ21
Zvezek: ǂiss. ǂ4
Čas izdaje: 2016
DOI: 10.3390/molecules21040410
ID: 13390856