脂肪生成
内分泌学
内科学
化学
脂肪组织
血脂异常
脂肪细胞
甘油三酯
2型糖尿病
兴奋剂
胰岛素抵抗
脂蛋白
胆固醇
糖尿病
药理学
受体
生物化学
生物
医学
作者
Luiz Antônio Dutra,Mariella Guimarães Lacerda,Maiara Destro Inácio,Johnny Wallef Leite Martins,Ana C. Lopes Silva,Patrícia Bento da Silva,Marlus Chorilli,Angélica Amorim Amato,Amanda Martins Baviera,Marisa Passarelli,Rafael Victório Carvalho Güido,Jean Leandro dos Santos
标识
DOI:10.1016/j.bioorg.2022.105600
摘要
Peroxisome proliferator-activated receptors are promising therapeutic targets for metabolic diseases, including obesity, diabetes, and dyslipidemia. This study describes the design, synthesis and pharmacological evaluation of stilbene-based compounds as dual PPARα/γ partial agonists with potency in the nanomolar range. In vitro and in vivo assays revealed that the lead compound (E)-4-styrylphenoxy-propanamide (5b) removed 14C-cholesterol from the foam cells through apolipoprotein A-I and High-Density Lipoprotein-2. In the high-fat diet-induced obesity mouse model, the oral administration of compound 5b increased HDL levels, paraoxonase-1 activity, and insulin sensitivity, and decreased glucose levels. Moreover, the adipogenesis pathway and triglyceride accumulation slightly changed in the adipocyte cells upon treatment with compound 5b, without affecting the body weight and adipose tissue in obese mice. Compound 5b did not affect the plasma levels of hepatic and renal injury biomarkers. Thus, stilbene-based compound 5b is a promising prototype for developing novel candidates to treat dyslipidemia and diabetes.
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