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作为代谢综合征潜在治疗药物的格列酮类含萜类似物。

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

作者信息

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

机构信息

N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 630090 Novosibirsk, Russia.

出版信息

Curr Issues Mol Biol. 2023 Mar 8;45(3):2230-2247. doi: 10.3390/cimb45030144.

Abstract

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) 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.

摘要

代谢综合征是一种涉及葡萄糖和脂质代谢受损的复杂异常情况,需要有效的药物治疗。降低与此病理相关的脂质和葡萄糖水平的一种方法是同时激活核PPAR-α和γ。为此,我们基于格列酮类药物的药效团片段合成了一些潜在激动剂,并在分子结构中引入了单萜或二萜部分。对肥胖和2型糖尿病(C57Bl/6)小鼠的药理活性研究表明,有一种物质能够通过增强肝脏和脂肪组织中甘油三酯的分解代谢来降低其水平,并表现出与小鼠组织对胰岛素的敏感性相关的降血糖作用。此外,该物质对肝脏没有毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2fb/10047834/7b9f2854c14e/cimb-45-00144-g001.jpg

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