甘草酸及其衍生物抗肿瘤和癌症化学预防作用，起效机制和细胞结构毒性关系

Title:Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship

Volume: 23 Issue: 5

Author(s): Ali Roohbakhsh, Milad Iranshahy, Mehrdad Iranshahi

Affiliation:

关键词: 甘草次酸，生胃酮，甘草素，光果甘草，甘草、18α-甘草次酸，18β-甘草次酸

摘要: 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-β-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 µM. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC₅₀s ≤ 1 µM. Studies have shown that the introduction of a double bound at the C₁-C₂ position combined with an electronegative functional group, such as CN, CF₃ or iodine at C₂ position, and the oxidation of the hydroxyl group of C₃ to the carbonyl group, significantly increased cytotoxicity. This review describes the cytotoxic and anti-tumor properties of GA and its derivatives, targets and mechanisms of action and provides insight into the structure-activity relationship of GA derivatives.

Cite this article as:

Ali Roohbakhsh, Milad Iranshahy, Mehrdad Iranshahi , Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship, Current Medicinal Chemistry 2016; 23 (5) . https://dx.doi.org/10.2174/0929867323666160112122256