Moldes-Anaya Angel, Sæther Thomas, Uhlig Silvio, Nebb Hilde I, Larsen Terje, Eilertsen Hans C, Paulsen Steinar M
Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, 9019 Tromsø, Norway.
MabCent-SFI, UiT The Arctic University of Norway, 9019 Tromsø, Norway.
Mar Drugs. 2017 May 25;15(6):148. doi: 10.3390/md15060148.
The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug targets. However, for several of the PPAR drugs currently in use, adverse side effects have been reported. In an effort to identify compounds from marine organisms that may serve as molecular scaffolds for the development of novel and safer PPAR-targeting drugs, we performed a bioassay-guided screening of organic extracts made from organisms supplied by the Norwegian Biobank of Arctic Marine Organisms (Marbank). Among several interesting hits, we identified two poorly described isomeric oxo-fatty acids from the microalgae for which we provide the first evidence that they might display dual specificity towards human PPARα and PPARγ. Principal component analysis showed that stood out from other species, both with respect to the metabolic profile and the PPAR activity. The isolation of these compounds holds the potential of uncovering a PPAR pharmacophore with tunable activity and specificity.
过氧化物酶体增殖物激活受体（PPARs）作为配体激活的转录因子发挥作用，通过激活代谢靶基因将脂质形式的信号转化为生理反应。由于其在脂质和碳水化合物代谢中的关键作用，PPARs是重要的药物靶点。然而，对于目前正在使用的几种PPAR药物，已经报道了不良副作用。为了从海洋生物中鉴定出可能作为开发新型、更安全的PPAR靶向药物的分子支架的化合物，我们对挪威北极海洋生物生物库（Marbank）提供的生物样本的有机提取物进行了生物测定指导的筛选。在几个有趣的活性物质中，我们从微藻中鉴定出两种描述较少的异构氧代脂肪酸，我们首次提供证据表明它们可能对人PPARα和PPARγ具有双重特异性。主成分分析表明，无论是在代谢谱还是PPAR活性方面，该微藻都与其他物种不同。这些化合物的分离有可能揭示一种具有可调节活性和特异性的PPAR药效团。
