Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Bioorg Med Chem Lett. 2013 Sep 1;23(17):4813-6. doi: 10.1016/j.bmcl.2013.06.101. Epub 2013 Jul 10.
In a previous study, retrofractamide A from the fruit of Piper chaba was shown to promote adipogenesis in 3T3-L1 cells. In the present study, retrofractamide A and its derivatives were synthesized, and their adipogenetic effects in 3T3-L1 cells were examined. Among the tested compounds, an amide composed of 9-(3',4'-methylenedioxyphenyl)-nona-2E,4E,8E-trienoic acid and an n-butyl or n-pentyl amine showed strongest activity. Moreover, the amide with the n-pentyl amine moiety significantly increased the uptake of 2-deoxyglucose into the cells, and also increased the mRNA levels of adiponectin, peroxisome proliferator-activated receptor γ2 (PPARγ2), glucose transporter 4 (GLUT4), fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein (C/EBP) α and β in a similar manner as the PPARγ agonist troglitazone, although it had less agonistic activity against PPARγ.
在之前的研究中，已证实荜澄茄中的反式裂环烯醚萜酰胺 A 可促进 3T3-L1 细胞的脂肪生成。在本研究中，合成了反式裂环烯醚萜酰胺 A 及其衍生物，并检测了它们在 3T3-L1 细胞中的脂肪生成作用。在所测试的化合物中，由 9-(3',4'-亚甲二氧基苯基）-壬-2E,4E,8E-三烯酸和正丁胺或正戊胺组成的酰胺显示出最强的活性。此外，具有正戊胺部分的酰胺可显著增加细胞对 2-脱氧葡萄糖的摄取，并且还以类似于 PPARγ 激动剂曲格列酮的方式增加了脂联素、过氧化物酶体增殖物激活受体 γ2 (PPARγ2)、葡萄糖转运蛋白 4 (GLUT4)、脂肪酸结合蛋白 (aP2) 和 CCAAT/增强子结合蛋白 (C/EBP) α 和 β 的 mRNA 水平，尽管它对 PPARγ 的激动活性较弱。
