Synthesis and biochemical evaluation of warhead-decorated psoralens as (immuno)proteasome inhibitors

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

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 (β5i) 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 β5i 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.

• Jezik: Angleški jezik
• Ključne besede: immunoproteasome, psoralen core, non-peptidic, electrophilic compounds, warhead scan
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 18 str.
• Številčenje: Vol. 26, iss. 2, art. 356
• PID: 20.500.12556/RUL-134920
• UDK: 615.4:54:616-097
• ISSN pri članku: 1420-3049
• DOI: 10.3390/molecules26020356
• COBISS.SI-ID: 46540803
• Datum objave v RUL: 11.02.2022

Gradivo je del revije

• Naslov: Molecules
• Skrajšan naslov: Molecules
• Založnik: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 12.01.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: imunopreoteasom, zaviralci, psoralen, avtoimunske bolezni, farmacevtska kemija