Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500 046, India.
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6160-5. doi: 10.1016/j.bmcl.2012.08.017. Epub 2012 Aug 9.
An improved synthesis of functionalized aurones has been accomplished via the reaction of benzofuran-3(2H)-one with a range of benzaldehydes in the presence of a mild base EDDA under ultrasound. A number of aurones were synthesized (within 5-30min) and the molecular structure of a representative compound determined by single crystal X-ray diffraction study confirmed Z-geometry of the C-C double bond present within the molecule. Some of the compounds synthesized have shown SIRT1 inhibiting as well as anti proliferative properties against two cancer cell lines in vitro. Compound 3a [(Z)-2-(5-bromo-2-hydroxybenzylidene) benzofuran-3(2H)-one] was identified as a potent inhibitor of SIRT1 (IC(50)=1μM) which showed a dose dependent increase in the acetylation of p53 resulting in induction of apoptosis.
通过在超声条件下，用温和的碱 EDDA 使苯并呋喃-3(2H)-酮与一系列苯甲醛反应，实现了功能化奥酮的改进合成。合成了许多奥酮（5-30 分钟内），并通过单晶 X 射线衍射研究确定了一个代表性化合物的分子结构，证实了分子中存在的 C-C 双键的 Z-几何构型。一些合成的化合物已显示出对两种体外癌细胞系的 SIRT1 抑制作用和抗增殖特性。化合物 3a [(Z)-2-(5-溴-2-羟基苯亚甲基)苯并呋喃-3(2H)-酮]被鉴定为 SIRT1 的有效抑制剂（IC50=1μM），它可使 p53 的乙酰化呈剂量依赖性增加，从而诱导细胞凋亡。
