Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome
The constitutive proteasome and the immunoproteasome represent validated targets for pharmacological intervention in the context of various diseases, such as cancer, inflammation, and autoimmune diseases. The development of novel chemical scaffolds of non-peptidic nature, capable of inhibiting diffe...
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| Format: | Article |
| Language: | English |
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Sciendo
2023-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2023-0032 |
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| _version_ | 1832546390306193408 |
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| author | Gobec Martina Obreza Aleš Jukič Marko Baumgartner Ana Mihelčič Nja Potočnik Špela Virant Julija Mlinarič Irena Stanislav Raščan Sosič Gobec Izidor |
| author_facet | Gobec Martina Obreza Aleš Jukič Marko Baumgartner Ana Mihelčič Nja Potočnik Špela Virant Julija Mlinarič Irena Stanislav Raščan Sosič Gobec Izidor |
| author_sort | Gobec Martina |
| collection | DOAJ |
| description | The constitutive proteasome and the immunoproteasome represent validated targets for pharmacological intervention in the context of various diseases, such as cancer, inflammation, and autoimmune diseases. The development of novel chemical scaffolds of non-peptidic nature, capable of inhibiting different catalytically active subunits of both isoforms, is a viable approach against these diseases. Such compounds are also useful as leads for the development of biochemical probes that enable the studies of the roles of both isoforms in various biological contexts. Here, we present a ligand-based computational design of (immuno)proteasome inhibitors, which resulted in the amino-substituted N-arylpiperidine-based compounds that can inhibit different subunits of the (immuno)proteasome in the low micromolar range. The compounds represent a useful starting point for further structure-activity relationship studies that will, hopefully, lead to non-peptidic compounds that could be used in pharmacological and biochemical studies of both proteasomes. |
| format | Article |
| id | doaj-art-3dd9d6d3477b4fc687b11f8c5decf146 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-3dd9d6d3477b4fc687b11f8c5decf1462025-02-03T06:59:25ZengSciendoActa Pharmaceutica1846-95582023-09-0173344145610.2478/acph-2023-0032Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasomeGobec Martina0Obreza Aleš1Jukič Marko2Baumgartner Ana3Mihelčič Nja4Potočnik Špela5Virant Julija6Mlinarič Irena7Stanislav Raščan8Sosič Gobec Izidor9University of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000Ljubljana, SloveniaThe constitutive proteasome and the immunoproteasome represent validated targets for pharmacological intervention in the context of various diseases, such as cancer, inflammation, and autoimmune diseases. The development of novel chemical scaffolds of non-peptidic nature, capable of inhibiting different catalytically active subunits of both isoforms, is a viable approach against these diseases. Such compounds are also useful as leads for the development of biochemical probes that enable the studies of the roles of both isoforms in various biological contexts. Here, we present a ligand-based computational design of (immuno)proteasome inhibitors, which resulted in the amino-substituted N-arylpiperidine-based compounds that can inhibit different subunits of the (immuno)proteasome in the low micromolar range. The compounds represent a useful starting point for further structure-activity relationship studies that will, hopefully, lead to non-peptidic compounds that could be used in pharmacological and biochemical studies of both proteasomes.https://doi.org/10.2478/acph-2023-0032proteasomesscaffold morphingoptimizationcomputational designselectivityinhibitors |
| spellingShingle | Gobec Martina Obreza Aleš Jukič Marko Baumgartner Ana Mihelčič Nja Potočnik Špela Virant Julija Mlinarič Irena Stanislav Raščan Sosič Gobec Izidor Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome Acta Pharmaceutica proteasomes scaffold morphing optimization computational design selectivity inhibitors |
| title | Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome |
| title_full | Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome |
| title_fullStr | Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome |
| title_full_unstemmed | Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome |
| title_short | Design and synthesis of amino-substituted N-arylpiperidinyl-based inhibitors of the (immuno)proteasome |
| title_sort | design and synthesis of amino substituted n arylpiperidinyl based inhibitors of the immuno proteasome |
| topic | proteasomes scaffold morphing optimization computational design selectivity inhibitors |
| url | https://doi.org/10.2478/acph-2023-0032 |
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