BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Planta Med. 2010 Jul;76(10):1011-4. doi: 10.1055/s-0029-1240863. Epub 2010 Feb 22.
Silent information regulator two ortholog 1 (SIRT1) is a member of the sirtuin deacetylase family of enzymes that removes acetyl groups from the lysine residues in histones and other proteins. It has been suggested that SIRT1 inhibitors might be beneficial in the treatment of cancer and neurodegenerative diseases. Bioassay-guided fractionation of the MeOH extract of the leaves of CROTON TONKINENSIS resulted in the isolation of a new ENT-kaurane diterpenoid (1) along with 11 known compounds (2- 12). The structure of the new compound 1 was determined to be ENT-11 alpha-acetoxy-7 beta-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 6- 9, 11, and 12 exhibited SIRT1 inhibitory activity in an IN VITRO assay, with IC (50) values ranging from 16.08 +/- 0.11 to 44.34 +/- 2.32 microM. This is the first report showing the potential of ENT-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.
沉默信息调节因子 2 同源物 1（SIRT1）是去乙酰化酶家族的一种酶，可从组蛋白和其他蛋白质的赖氨酸残基上去除乙酰基。有人提出，SIRT1 抑制剂可能有益于癌症和神经退行性疾病的治疗。对 CROTON TONKINENSIS 叶的甲醇提取物进行生物测定指导的分步分离，得到了一个新的 ENT-贝壳杉烷二萜（1）以及 11 个已知化合物（2-12）。根据光谱分析，新化合物 1 的结构被确定为 ENT-11α-乙酰氧基-7β-羟基贝壳杉-16-烯-15-酮。化合物 3、4、6-9、11 和 12 在体外测定中表现出 SIRT1 抑制活性，IC（50）值范围为 16.08±0.11 至 44.34±2.32μM。这是首次报道 ENT-贝壳杉烷二萜作为一类新的天然 SIRT1 抑制剂的潜力。
