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Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synt...

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Autores principales: Blokhin, Mikhail E., Kuranov, Sergey O., Khvostov, Mikhail V., Fomenko, Vladislav V., Luzina, Olga A., Zhukova, Natalia A., Elhajjar, Cham, Tolstikova, Tatiana G., Salakhutdinov, Nariman F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047834/
https://www.ncbi.nlm.nih.gov/pubmed/36975514
http://dx.doi.org/10.3390/cimb45030144
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author Blokhin, Mikhail E.
Kuranov, Sergey O.
Khvostov, Mikhail V.
Fomenko, Vladislav V.
Luzina, Olga A.
Zhukova, Natalia A.
Elhajjar, Cham
Tolstikova, Tatiana G.
Salakhutdinov, Nariman F.
author_facet Blokhin, Mikhail E.
Kuranov, Sergey O.
Khvostov, Mikhail V.
Fomenko, Vladislav V.
Luzina, Olga A.
Zhukova, Natalia A.
Elhajjar, Cham
Tolstikova, Tatiana G.
Salakhutdinov, Nariman F.
author_sort Blokhin, Mikhail E.
collection PubMed
description Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6(Ay)) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.
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spelling pubmed-100478342023-03-29 Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome Blokhin, Mikhail E. Kuranov, Sergey O. Khvostov, Mikhail V. Fomenko, Vladislav V. Luzina, Olga A. Zhukova, Natalia A. Elhajjar, Cham Tolstikova, Tatiana G. Salakhutdinov, Nariman F. Curr Issues Mol Biol Article Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6(Ay)) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver. MDPI 2023-03-08 /pmc/articles/PMC10047834/ /pubmed/36975514 http://dx.doi.org/10.3390/cimb45030144 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Blokhin, Mikhail E.
Kuranov, Sergey O.
Khvostov, Mikhail V.
Fomenko, Vladislav V.
Luzina, Olga A.
Zhukova, Natalia A.
Elhajjar, Cham
Tolstikova, Tatiana G.
Salakhutdinov, Nariman F.
Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title_full Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title_fullStr Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title_full_unstemmed Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title_short Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome
title_sort terpene-containing analogues of glitazars as potential therapeutic agents for metabolic syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047834/
https://www.ncbi.nlm.nih.gov/pubmed/36975514
http://dx.doi.org/10.3390/cimb45030144
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