Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions
Cannabinoid ligands are known to possess neuroprotective actions and may have utility in the treatment of neurodegeneration. The major targets for cannabinoids include the classical CB1 cannabinoid receptor, as well as the novel cannabinoid receptor GPR55 which binds to many synthetic cannabinoid li...
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2023-02-01
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Series: | The Ukrainian Biochemical Journal |
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Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2023/04/Senkiv_95_1.pdf |
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author | J. Senkiv A. Kryshchyshyn-Dylevych D. Khylyuk M. Wujec R. Stoika A. J. Irving R. Lesyk |
author_facet | J. Senkiv A. Kryshchyshyn-Dylevych D. Khylyuk M. Wujec R. Stoika A. J. Irving R. Lesyk |
author_sort | J. Senkiv |
collection | DOAJ |
description | Cannabinoid ligands are known to possess neuroprotective actions and may have utility in the treatment of neurodegeneration. The major targets for cannabinoids include the classical CB1 cannabinoid receptor, as well as the novel cannabinoid receptor GPR55 which binds to many synthetic cannabinoid ligands. In this study, novel thiopyranothiazoles 1, 3, 4, 6, and 7 were synthesized and their pharmacological activity as potential cannabinoid-like ligands was evaluated in glioblastoma cells, cultured cortical neurons, and cells of HEK293 line expressing GPR55. Stimulation of protein kinase ERK1/2, MAP-kinases and cAMP response element binding protein (CREB) was evaluated using Western-blot analysis. CREB activation was additionally monitored by means of confocal imaging of nuclear phospho-CREB labeling. Docking simulation confirmed the good affinity of the synthesized compounds to CB1 and CB2 receptors. Striking effects of the chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol with ethylacetate moiety (3) and isothiochromeno[4a,4-d]thiazole with phenazone fragment (7) on pCREB activation as the indicator of stimulation of the pathway beneficial for neurons survival were observed. |
first_indexed | 2024-03-11T18:12:32Z |
format | Article |
id | doaj.art-bdb3db9398744c3fb8c066fadd314083 |
institution | Directory Open Access Journal |
issn | 2409-4943 2413-5003 |
language | English |
last_indexed | 2024-03-11T18:12:32Z |
publishDate | 2023-02-01 |
publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
record_format | Article |
series | The Ukrainian Biochemical Journal |
spelling | doaj.art-bdb3db9398744c3fb8c066fadd3140832023-10-16T11:32:19ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032023-02-01951314310.15407/ubj95.01.031Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functionsJ. Senkiv0https://orcid.org/0000-0002-0587-3850A. Kryshchyshyn-Dylevych1https://orcid.org/0000-0002-8713-7020D. Khylyuk2https://orcid.org/0000-0001-9306-7463M. Wujec3https://orcid.org/0000-0001-9816-1934R. Stoika4https://orcid.org/0000-0001-5719-2187A. J. Irving5R. Lesyk6Department of Regulation Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences of Ukraine, LvivDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Lviv, UkraineDepartment of Organic Chemistry, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Lublin, PolandDepartment of Organic Chemistry, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Lublin, PolandDepartment of Regulation Cell Proliferation and Apoptosis, Institute of Cell Biology, National Academy of Sciences of Ukraine, LvivSchool of Biomedical and Biomolecular Science, University College of Dublin, Dublin, IrelandDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine; Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Rzeszow, PolandCannabinoid ligands are known to possess neuroprotective actions and may have utility in the treatment of neurodegeneration. The major targets for cannabinoids include the classical CB1 cannabinoid receptor, as well as the novel cannabinoid receptor GPR55 which binds to many synthetic cannabinoid ligands. In this study, novel thiopyranothiazoles 1, 3, 4, 6, and 7 were synthesized and their pharmacological activity as potential cannabinoid-like ligands was evaluated in glioblastoma cells, cultured cortical neurons, and cells of HEK293 line expressing GPR55. Stimulation of protein kinase ERK1/2, MAP-kinases and cAMP response element binding protein (CREB) was evaluated using Western-blot analysis. CREB activation was additionally monitored by means of confocal imaging of nuclear phospho-CREB labeling. Docking simulation confirmed the good affinity of the synthesized compounds to CB1 and CB2 receptors. Striking effects of the chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol with ethylacetate moiety (3) and isothiochromeno[4a,4-d]thiazole with phenazone fragment (7) on pCREB activation as the indicator of stimulation of the pathway beneficial for neurons survival were observed.http://ukrbiochemjournal.org/wp-content/uploads/2023/04/Senkiv_95_1.pdfcamp response element binding protein (creb)cb1cb2cultured cortical neuronsputative cannabinoid ligandsthiopyranothiazoles |
spellingShingle | J. Senkiv A. Kryshchyshyn-Dylevych D. Khylyuk M. Wujec R. Stoika A. J. Irving R. Lesyk Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions The Ukrainian Biochemical Journal camp response element binding protein (creb) cb1 cb2 cultured cortical neurons putative cannabinoid ligands thiopyranothiazoles |
title | Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions |
title_full | Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions |
title_fullStr | Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions |
title_full_unstemmed | Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions |
title_short | Novel putative ligands of cannabinoid receptors: synthesis and effects on cell signaling and neuronal functions |
title_sort | novel putative ligands of cannabinoid receptors synthesis and effects on cell signaling and neuronal functions |
topic | camp response element binding protein (creb) cb1 cb2 cultured cortical neurons putative cannabinoid ligands thiopyranothiazoles |
url | http://ukrbiochemjournal.org/wp-content/uploads/2023/04/Senkiv_95_1.pdf |
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