Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
Eur J Pharmacol. 2015 Feb 5;748:61-7. doi: 10.1016/j.ejphar.2014.12.009. Epub 2014 Dec 18.
Resveratrol is a polyphenol found in grapes and red wine, showing well-characterized anti-inflammatory and antiproliferative activities. In order to exceed resveratrol׳s biological effects and to reveal the structural determinants of the molecule׳s activity, numerous derivatives were synthesized recently. Most of these resveratrol analogs vary from the original molecule in the number, position or identity of the phenolic functional groups. Investigation of the analogs provided important data regarding structure-activity relationship of the molecule. With the exception of cis- and trans-resveratrol and the reduced form dihydroresveratrol, little is known about the molecular effects of the stilbene backbone. In the present study we investigated the anti-inflammatory properties of a new, triple-bond resveratrol analog, 3,4',5-trihydroxy-diphenylacetylene (TDPA) on lipopolysaccharide-stimulated RAW macrophages. We found that the analog had weaker antioxidant activity and stronger inhibitory effect on nuclear factor-kappaB activation, and on cyclooxygenase-2, tumor necrosis factor α and interleukin-6 production. It also prevented lipopolysaccharide-induced depolarization of the mitochondrial membrane. In contrast to resveratrol, TDPA increased the phosphorylation of c-Jun N-terminal and p38 mitogen activated protein kinases. In summary, we identified a novel compound with better anti-inflammatory properties than resveratrol. Our results contributed to a better understanding of the structural determinants of resveratrol׳s biological activities.
白藜芦醇是一种存在于葡萄和红酒中的多酚，具有明确的抗炎和抗增殖活性。为了超越白藜芦醇的生物学效应，并揭示分子活性的结构决定因素，最近合成了许多衍生物。这些白藜芦醇类似物大多数在酚类官能团的数量、位置或种类上与原始分子不同。对这些类似物的研究提供了关于分子结构-活性关系的重要数据。除顺式和反式白藜芦醇以及还原形式二氢白藜芦醇外，对芪骨架的分子效应知之甚少。在本研究中，我们研究了新型三键白藜芦醇类似物 3,4',5-三羟基二苯乙炔（TDPA）对脂多糖刺激的 RAW 巨噬细胞的抗炎特性。我们发现该类似物具有较弱的抗氧化活性，对核因子-κB 激活以及环氧合酶-2、肿瘤坏死因子α和白细胞介素-6 的产生具有更强的抑制作用。它还可以防止脂多糖诱导的线粒体膜去极化。与白藜芦醇不同，TDPA 增加了 c-Jun N 端和 p38 丝裂原活化蛋白激酶的磷酸化。总之，我们鉴定出一种具有比白藜芦醇更好抗炎特性的新型化合物。我们的研究结果有助于更好地理解白藜芦醇生物学活性的结构决定因素。
