Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure-Cytotoxic Activity Relationship
Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure-Cytotoxic Activity Relationship
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DOI：
10.2174/0929867323666160112122256
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
Iranshahi, Mehrdad
中科院分区：
文献类型：
--
作者：
Roohbakhsh, Ali;Iranshahy, Milad;Iranshahi, Mehrdad
抗肿瘤的特性已被归因于，至少部分地，对甘草甜素（GL）。然而，GL不直接通过胃肠道吸收。它被人体肠道微生物菌群水解为18-β-大黄酸（GA），这是一种具有生物活性的代谢产物。GA具有显著的细胞毒性和抗肿瘤特性。在过去的十年里，GA的促凋亡靶点和作用机制已得到广泛研究。此外，GA是一种廉价且可用的三萜，其结构中具有官能团（COOH和OH），这使其成为药物化学家制备大量类似物的有吸引力的先导化合物。迄今为止，基于GA支架已经制备了400多种细胞毒性衍生物，其中IC 50值小于30 μ M的细胞毒性衍生物有128种。研究人员还成功地合成了具有IC（50）的非常有效的细胞毒性衍生物
The anti-cancer properties of liquorice have been attributed, at least in part, to glycyrrhizin (GL). However, GL is not directly absorbed through the gastrointestinal tract. It is hydrolyzed to 18-beta-glycyrrhetinic acid (GA), the pharmacologically active metabolite, by human intestinal microflora. GA exhibits remarkable cytotoxic and anti-tumor properties. The pro-apoptotic targets and mechanisms of action of GA have been extensively studied over the past decade. In addition, GA is an inexpensive and available triterpene with functional groups (COOH and OH) in its structure, which make it an attractive lead compound for medicinal chemists to prepare a large number of analogues. To date, more than 400 cytotoxic derivatives have been prepared on the basis of GA scaffold, including 128 cytotoxic derivatives with IC50 values less than 30 mu M. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC(50)s