Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain
Impact Factor: - 2023 (2024 update): 6.8
| Main Authors: | , , , , , , , , |
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| Format: | info:eu-repo/semantics/publishedVersion |
| Language: | eng |
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2024
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| Online Access: | http://hdl.handle.net/11086/552780 https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.4c00854 https://pubmed.ncbi.nlm.nih.gov/38858308/ |
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| author | Gómez Bouzó, Uxía Peluso Iltis, Carole Santalla, Hugo Quevedo, Mario Alfredo Verlinden, Lieve Verstuyf, Annemieke Fall, Yagamare Gómez, Generosa Rochel, Natacha |
| author2 | https://orcid.org/0000-0001-9913-8728 |
| author_facet | https://orcid.org/0000-0001-9913-8728 Gómez Bouzó, Uxía Peluso Iltis, Carole Santalla, Hugo Quevedo, Mario Alfredo Verlinden, Lieve Verstuyf, Annemieke Fall, Yagamare Gómez, Generosa Rochel, Natacha |
| author_sort | Gómez Bouzó, Uxía |
| collection | Repositorio Digital Universitario |
| description | Impact Factor: - 2023 (2024 update): 6.8 |
| format | info:eu-repo/semantics/publishedVersion |
| id | rdu-unc.552780 |
| institution | Universidad Nacional de Cordoba |
| language | eng |
| publishDate | 2024 |
| record_format | dspace |
| spelling | rdu-unc.5527802024-07-22T06:21:16Z Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain Gómez Bouzó, Uxía Peluso Iltis, Carole Santalla, Hugo Quevedo, Mario Alfredo Verlinden, Lieve Verstuyf, Annemieke Fall, Yagamare Gómez, Generosa Rochel, Natacha https://orcid.org/0000-0001-9913-8728 https://orcid.org/0000-0001-9550-9448 https://orcid.org/0000-0002-3573-5889 https://orcid.org/0000-0002-9467-1280 https://orcid.org/0000-0002-0808-198X https://orcid.org/0000-0003-3193-2698 https://orcid.org/0000-0002-9621-3662 Hydrocarbons Hydroxyls Ligands Noncovalent interactions Organic compounds Impact Factor: - 2023 (2024 update): 6.8 info:eu-repo/semantics/publishedVersion Fil: Gómez-Bouzó, Uxía. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Peluso-Iltis Carole. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch; France. Fil: Peluso-Iltis Carole. CNRS UMR 7104, Illkirch; France. Fil: Peluso-Iltis Carole. Inserm U1258, Illkirch; France. Fil: Peluso-Iltis Carole. University of Strasbourg, Illkirch; France. Fil: Santalla, Hugo. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Quevedo, Mario Alfredo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina. Fil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y desarrollo en Tecnología Farmacéutica; Argentina. Fil. Verlinden, Lieve. Clinical and Experimental Endocrinology: Department of Chronic Diseases and Metabolism, Leuven; Belgium. Fil: Verstuyf, Annemieke. Clinical and Experimental Endocrinology: Department of Chronic Diseases and Metabolism, Leuven; Belgium. Fil: Fall, Yagamare. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Gómez, Generosa. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Rochel, Natacha. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch; France. Fil: Rochel, Natacha. CNRS UMR 7104, Illkirch; France. Fil: Rochel, Natacha. Inserm U1258, Illkirch; France. Fil: Rochel, Natacha. University of Strasbourg, Illkirch; France. We synthesized two new gemini analogues, UG-480 and UG-481, that incorporate a modified longer side chain containing a cyclopropane group. The evaluation of the bioactivities of the two gemini analogues indicated that the 17,20 threo (20S) compound, UG-480, is the most active one and is as active as 1,25(OH)2D3. Docking and molecular dynamics (MD) data showed that the compounds bind efficiently to vitamin D receptor (VDR) with UG-480 to form an energetically more favorable interaction with His397. Structural analysis indicated that whereas the UG-480 compound efficiently stabilizes the active VDR conformation, it induces conformational changes in the H6–H7 VDR region that are greater than those induced by the parental Gemini and that this is due to the occupancy of the secondary channel by its modified side chain. info:eu-repo/semantics/publishedVersion Fil: Gómez-Bouzó, Uxía. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Peluso-Iltis Carole. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch; France. Fil: Peluso-Iltis Carole. CNRS UMR 7104, Illkirch; France. Fil: Peluso-Iltis Carole. Inserm U1258, Illkirch; France. Fil: Peluso-Iltis Carole. University of Strasbourg, Illkirch; France. Fil: Santalla, Hugo. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Quevedo, Mario Alfredo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina. Fil: Quevedo, Mario Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y desarrollo en Tecnología Farmacéutica; Argentina. Fil. Verlinden, Lieve. Clinical and Experimental Endocrinology: Department of Chronic Diseases and Metabolism, Leuven; Belgium. Fil: Verstuyf, Annemieke. Clinical and Experimental Endocrinology: Department of Chronic Diseases and Metabolism, Leuven; Belgium. Fil: Fall, Yagamare. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Gómez, Generosa. Universidad de Vigo. Departamento de Química Orgánica and Instituto de Investigación Sanitaría Galicia; Spain. Fil: Rochel, Natacha. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch; France. Fil: Rochel, Natacha. CNRS UMR 7104, Illkirch; France. Fil: Rochel, Natacha. Inserm U1258, Illkirch; France. Fil: Rochel, Natacha. University of Strasbourg, Illkirch; France. 2024-07-21T19:44:42Z 2024-07-21T19:44:42Z 2024-06-10 article Gómez-Bouzó, U., Peluso-Iltis, C., Santalla, H., Quevedo, M. A., Verlinden, L., Verstuyf, A., ... & Rochel, N. (2024). Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain. Journal of Medicinal Chemistry. http://hdl.handle.net/11086/552780 1520-4804 https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.4c00854 https://pubmed.ncbi.nlm.nih.gov/38858308/ doi.org/10.1021/acs.jmedchem.4c00854 eng Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | Hydrocarbons Hydroxyls Ligands Noncovalent interactions Organic compounds Gómez Bouzó, Uxía Peluso Iltis, Carole Santalla, Hugo Quevedo, Mario Alfredo Verlinden, Lieve Verstuyf, Annemieke Fall, Yagamare Gómez, Generosa Rochel, Natacha Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title | Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title_full | Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title_fullStr | Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title_full_unstemmed | Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title_short | Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain |
| title_sort | design synthesis and biological evaluation of new type of gemini analogues with a cyclopropane moiety in their side chain |
| topic | Hydrocarbons Hydroxyls Ligands Noncovalent interactions Organic compounds |
| url | http://hdl.handle.net/11086/552780 https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.4c00854 https://pubmed.ncbi.nlm.nih.gov/38858308/ |
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