Studies on chemical modification and biology of a natural product, gambogic acid (III): Determination of the essential pharmacophore for biological activity
Studies on chemical modification and biology of a natural product, gambogic acid (III): Determination of the essential pharmacophore for biological activity
复制标题
天然产物藤黄酸的化学修饰和生物学研究（III）：生物活性必需药效基团的测定
DOI：
10.1016/j.ejmech.2011.01.051
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发表时间：
2011-04-01
影响因子：
6.7
通讯作者：
You, Qidong
中科院分区：
文献类型：
--
作者：
Wang, Xiaojian;Lu, Na;You, Qidong
笼状4-氧杂-三环[4.3.1.0(3，7)]DEC-2-酮结构模体在藤黄天然产物中发现，具有抗肿瘤活性。藤黄酸(GA，1)是笼养藤黄中含量最高的一种化合物，被认为是一种很有前途的抗癌药物。为了确定其抗肿瘤活性的基本药效团，合成了一系列针对潜在生物活性关键结构特征的GA类似物，其中化合物11a具有与GA相似的体外抗肿瘤活性。对透明质酸的机制研究表明，该化合物可诱导HepG2细胞凋亡，并阻止细胞周期的G2/M期。报道了在GA中发现的维持抗肿瘤作用的支架的关键部分的测定，以及基于笼形药效基团的SAR，将为未来的抗癌药物开发研究提供关键信息。(C)2011年爱思唯尔·马森公司。版权所有。
Caged 4-oxa-tricyclo[4.3.1.0(3,7)]dec-2-one structural motifs are found in Garcinia natural products that demonstrate anti-tumor activity. Gambogic acid (GA, 1), the most abundant caged Garcinia xanthones, has been reported to be a promising anti-cancer agent. To identify the essential pharmacophore for its anti-tumor activity, a series of GA analogues that address potential key structural features for biological activity were synthesized, among which compound 11a displayed comparable in vitro anti-tumor activity as GA. Mechanistic studies on ha determined that the compound induces apoptosis as well as arrests the G2/M phase of the cell cycle in HepG2 cells. The determination of the essential part of the scaffold found in GA to maintain anti-tumor effects, and the SAR based on the caged pharmacophore are reported and will provide key information for future anti-cancer drug development studies. (c) 2011 Elsevier Masson SAS. All rights reserved.