Tanini Damiano, Panzella Lucia, Amorati Riccardo, Capperucci Antonella, Pizzo Elio, Napolitano Alessandra, Menichetti Stefano, d'Ischia Marco
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Italy.
Org Biomol Chem. 2015 May 28;13(20):5757-64. doi: 10.1039/c5ob00193e. Epub 2015 Apr 22.
The structural modification of the resveratrol scaffold is currently an active issue in the quest for more potent and versatile antioxidant derivatives for biomedical applications. Disclosed herein is an expedient and efficient entry to a novel class of resveratrol derivatives featuring an unprecedented 2-phenylbenzoselenophene skeleton. The new compounds were obtained in good yields by direct selenenylation of resveratrol with Se(0) and SO2Cl2 in dry THF. Varying the [Se : SO2Cl2 : resveratrol] ratio resulted in the formation of the parent benzoselenophene (1) and/or mono (2) and/or dichloro (3) benzoselenophene derivatives. All the benzoselenophene derivatives proved to be more efficient than resveratrol in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays, with 1 showing an activity nearly comparable to that of Trolox. 1-3 also proved to be more efficient inhibitors than the parent resveratrol in kinetic experiments of styrene autoxidation. DFT calculations of the O-H bond dissociation enthalpy (BDE) revealed that the introduction of the Se-atom causes a significant decrease of the BDE of 3-OH and 5-OH, with just a small increase of the 4'-OH BDE. Compounds 1-3 showed no cytotoxicity at 5 μM concentrations on human keratinocyte (HaCaT) and intestinal (CaCo-2) cell lines.
白藜芦醇骨架的结构修饰是目前寻找更有效、更通用的生物医学应用抗氧化剂衍生物的一个活跃课题。本文公开了一种便捷高效的方法，可用于制备一类新型白藜芦醇衍生物，其具有前所未有的2-苯基苯并硒吩骨架。通过在干燥的四氢呋喃中用硒（0）和二氯亚砜对白藜芦醇进行直接硒化反应，以良好的产率得到了新化合物。改变[硒∶二氯亚砜∶白藜芦醇]的比例会导致母体苯并硒吩（1）和/或单氯（2）和/或二氯（3）苯并硒吩衍生物的形成。在2,2-二苯基-1-苦基肼基（DPPH）和铁还原/抗氧化能力（FRAP）测定中，所有苯并硒吩衍生物都比白藜芦醇更有效，其中1显示出与Trolox几乎相当的活性。在苯乙烯自动氧化的动力学实验中，1-3也被证明是比母体白藜芦醇更有效的抑制剂。对O-H键解离焓（BDE）的密度泛函理论计算表明，硒原子的引入导致3-OH和5-OH的BDE显著降低，而4'-OH的BDE仅略有增加。化合物1-3在5 μM浓度下对人角质形成细胞（HaCaT）和肠细胞（CaCo-2）系无细胞毒性。
