PPARα agonists based on stilbene and its bioisosteres: biological evaluation and docking studies
PPARα agonists based on stilbene and its bioisosteres: biological evaluation and docking studies
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DOI：
10.1039/c5md00151j
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Amoroso, Rosa
中科院分区：
文献类型：
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作者：
De Filippis, Barbara;Agamennone, Mariangela;Amoroso, Rosa
为了开发新的PPARα激动剂，合成并评价了一系列与反式二苯乙烯偶联的吉非罗齐类似物。通过在邻位或对位引入取代基来修饰二苯乙烯的苯基，只有远端环被萘基或杂芳基取代，保持了吉非罗齐的二甲基戊酸骨架不变。化合物5a和5d对PPARα调节基因CPT1a有较好的活性。对活性配体的结构研究强调了配体溶剂化能和疏水效应在决定PPARα活性中的主导作用。
A new series of gemfibrozil analogues conjugated with trans-stilbene were synthesized and evaluated with the aim of developing new PPAR alpha agonists. The phenyls of stilbene were modified by introducing substituents in the ortho or para position and only the distal ring was substituted with naphthyl or heteroaromatic moieties, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered. Two compounds, 5a and 5d, exhibited good activation of PPARa and were also screened for their activity on PPAR alpha-regulated gene CPT1A. Structure-based studies carried out on the active ligands highlighted the dominant role of ligand solvation energy and hydrophobic effect in determining the PPAR alpha activation.