Eva Shannon Schiffrer (Avtor), Matic Proj (Avtor), Martina Gobec (Avtor), Luka Rejc (Avtor), Andrej Šterman (Avtor), Janez Mravljak (Avtor), Stanislav Gobec (Avtor), Izidor Sosič (Avtor)

Povzetek

The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like ([beta]5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the [beta]5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure-activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors.

Ključne besede

imunopreoteasom;zaviralci;psoralen;immunoproteasome;psoralen core;non-peptidic;electrophilic compounds;warhead scan;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.4:54:616-097
COBISS: 46540803 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 193
Št. prenosov: 65
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: Avtoimunske bolezni;Farmacevtska kemija;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-18
Letnik: ǂVol. ǂ26
Zvezek: ǂiss. ǂ2
Čas izdaje: 2021
DOI: 10.3390/molecules26020356
ID: 14511489