Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
复制标题
发现五环三萜 3 β-酯衍生物作为一类新型胆固醇酯转移蛋白抑制剂
DOI：
10.1016/j.ejmech.2017.08.012
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发表时间：
2017-10-20
影响因子：
6.7
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Chen, Dongyin;Huang, Xin;Liu, Jun
设计、合成了一系列五环三萜313-酯衍生物，并对其作为一类新型胆固醇酯转移蛋白（CETP）抑制剂进行了评价。体外筛选结果表明，30个化合物中有5个化合物对人CETP活性有中等抑制作用，IC（50）小于10 μ M。其中，化合物20（IC 50 = 2.3 μ M）具有最强的生物活性，并且有效地改善人脂肪组织特异性CETP转基因（ap 2-CETPTg）小鼠和豚鼠的血浆脂质水平。另外的安全性评价（在豚鼠中没有血压升高）和药代动力学研究表明，化合物20的潜在可药用性是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。(C)2017年由Elsevier Masson SAS出版。
A series of pentacyclic triterpene 313-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC(50)s less than 10 mu M. Among them, compound 20 (IC50 = 2.3 mu M) had the most potent biological activity, and effectively ameliorated plasma lipid levels of human adipose tissue specific CETP transgenic (ap2-CETPTg) mice and guinea pigs. Additional safety evaluation (no blood pressure elevation in guinea pigs) and pharmacokinetics studies indicated that the potential druggability for compound 20 which is a promising lead for development of a new class of CETP inhibitors for the treatment of dyslipidemia. (C) 2017 Published by Elsevier Masson SAS.