20.500.12556/RUL-134920 Synthesis and biochemical evaluation of warhead-decorated psoralens as (immuno)proteasome inhibitors 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. immunoproteasome psoralen core non-peptidic electrophilic compounds warhead scan imunopreoteasom zaviralci psoralen avtoimunske bolezni farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-11 09:04:05 2022-02-11 09:04:10 2022-09-14 04:10:41 0000-00-00 00:00:00 2021 0 0 18 str. iss. 2, art. 356 Vol. 26 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:616-097 1420-3049 10.3390/molecules26020356 46540803 RAZ_Shannon_Schiffrer_Eva_2021.pdf RAZ_Shannon_Schiffrer_Eva_2021.pdf 1 F407D2A35BAAEE235946E9354770162A 032d1ef990236883f3c19de7486a94c9c31ff737fac84b027103b096e52930bc 98e52718-8b11-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153664 https://www.mdpi.com/1420-3049/26/2/356 0 f65a25a2-8b10-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153663 Fakulteta za farmacijo Fakulteta za kemijo in kemijsko tehnologijo 0 0 0