Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain

Autores
Gómez Bouzó, Uxía; Peluso Iltis, Carole; Santalla, Hugo; Quevedo, Mario Alfredo; Verlinden, Lieve; Verstuyf, Annemieke; Fall, Yagamare; Gómez, Generosa; Rochel, Natacha
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Impact Factor: - 2023 (2024 update): 6.8
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.
Materia
Hydrocarbons
Hydroxyls
Ligands
Noncovalent interactions
Organic compounds
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Repositorio Digital Universitario (UNC)
Institución
Universidad Nacional de Córdoba
OAI Identificador
oai:rdu.unc.edu.ar:11086/552780
Acceder
id RDUUNC_80a8a3e939c36065342ee7ef91ed139e
oai_identifier_str oai:rdu.unc.edu.ar:11086/552780
network_acronym_str RDUUNC
repository_id_str 2572
network_name_str Repositorio Digital Universitario (UNC)
spelling Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side ChainGómez Bouzó, UxíaPeluso Iltis, CaroleSantalla, HugoQuevedo, Mario AlfredoVerlinden, LieveVerstuyf, AnnemiekeFall, YagamareGómez, GenerosaRochel, NatachaHydrocarbonsHydroxylsLigandsNoncovalent interactionsOrganic compoundsImpact Factor: - 2023 (2024 update): 6.8Fil: 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/publishedVersionFil: 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.https://orcid.org/0000-0001-9913-8728https://orcid.org/0000-0001-9550-9448https://orcid.org/0000-0002-3573-5889https://orcid.org/0000-0002-9467-1280https://orcid.org/0000-0002-0808-198Xhttps://orcid.org/0000-0003-3193-2698https://orcid.org/0000-0002-9621-36622024-06-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfGómez-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/11086/5527801520-4804https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.4c00854https://pubmed.ncbi.nlm.nih.gov/38858308/https://doi.org/10.1021/acs.jmedchem.4c00854enginfo:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-09-29T13:41:23Zoai:rdu.unc.edu.ar:11086/552780Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-09-29 13:41:24.29Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse
dc.title.none.fl_str_mv 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
spellingShingle Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain
Gómez Bouzó, Uxía
Hydrocarbons
Hydroxyls
Ligands
Noncovalent interactions
Organic compounds
title_short 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_sort Design, Synthesis, and Biological Evaluation of New Type of Gemini Analogues with a Cyclopropane Moiety in Their Side Chain
dc.creator.none.fl_str_mv Gómez Bouzó, Uxía
Peluso Iltis, Carole
Santalla, Hugo
Quevedo, Mario Alfredo
Verlinden, Lieve
Verstuyf, Annemieke
Fall, Yagamare
Gómez, Generosa
Rochel, Natacha
author Gómez Bouzó, Uxía
author_facet Gómez Bouzó, Uxía
Peluso Iltis, Carole
Santalla, Hugo
Quevedo, Mario Alfredo
Verlinden, Lieve
Verstuyf, Annemieke
Fall, Yagamare
Gómez, Generosa
Rochel, Natacha
author_role author
author2 Peluso Iltis, Carole
Santalla, Hugo
Quevedo, Mario Alfredo
Verlinden, Lieve
Verstuyf, Annemieke
Fall, Yagamare
Gómez, Generosa
Rochel, Natacha
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv 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
dc.subject.none.fl_str_mv Hydrocarbons
Hydroxyls
Ligands
Noncovalent interactions
Organic compounds
topic Hydrocarbons
Hydroxyls
Ligands
Noncovalent interactions
Organic compounds
dc.description.none.fl_txt_mv Impact Factor: - 2023 (2024 update): 6.8
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.
description Impact Factor: - 2023 (2024 update): 6.8
publishDate 2024
dc.date.none.fl_str_mv 2024-06-10
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
status_str publishedVersion
format article
dc.identifier.none.fl_str_mv 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/
https://doi.org/10.1021/acs.jmedchem.4c00854
identifier_str_mv 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.
1520-4804
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/
https://doi.org/10.1021/acs.jmedchem.4c00854
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositorio Digital Universitario (UNC)
instname:Universidad Nacional de Córdoba
instacron:UNC
reponame_str Repositorio Digital Universitario (UNC)
collection Repositorio Digital Universitario (UNC)
instname_str Universidad Nacional de Córdoba
instacron_str UNC
institution UNC
repository.name.fl_str_mv Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdoba
repository.mail.fl_str_mv oca.unc@gmail.com
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score 13.070432

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