Salvador Jorge A R, Leal Ana S, Valdeira Ana S, Gonçalves Bruno M F, Alho Daniela P S, Figueiredo Sandra A C, Silvestre Samuel M, Mendes Vanessa I S
Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Coimbra, Portugal.
Michigan State University, Department of Pharmacology and Toxicology, Life Science Building 1355, Bogue St Room 430, USA.
Eur J Med Chem. 2017 Dec 15;142:95-130. doi: 10.1016/j.ejmech.2017.07.013. Epub 2017 Jul 14.
Natural pentacyclic triterpenoids (PTs) have been often reported to exhibit a wide range of biological activities. Among them, the anticancer and anti-inflammatory activities are the most studied. Over the last two decades, the number of publications reporting the anticancer effects of PTs has risen exponentially, reflecting the increasing interest in these natural products for the development of new antineoplastic drugs. Among of the most investigated PTs regarding their anticancer properties are oleanane-, ursane and friedelane-types, including oleanolic, glycyrrhetinic, ursolic and asiatic acids, and celastrol, among others. The extensive research in this field shows that the anticancer effects of PTs are mediated by several mechanisms, as they modulate a diverse range of molecular targets and signaling pathways, involved in cancer cell proliferation and survival. Considering the anticancer potential of this class of compounds, a number of semisynthetic derivatives has been synthetized aiming to improve their therapeutic activity and pharmacokinetic properties, and decrease their toxicity. Some of these new semisynthetic derivatives have shown improved anticancer activity in various cancer cell lines and animal models compared with the parent compound. Moreover, some of these compounds have been assessed in clinical trials, proving to be safe for human use. This review updates the most recent findings on the semisynthetic derivatives of oleanane-, ursane- and quinone methide friedelane-type PTs with anticancer activity. A brief introduction concerning the PTs and their anticancer activity is given, and the main semisynthetic modifications that have been performed between 2012 and early 2017 are reviewed and discussed.
天然五环三萜类化合物（PTs）常被报道具有广泛的生物活性。其中，抗癌和抗炎活性是研究最多的。在过去二十年中，报道PTs抗癌作用的出版物数量呈指数级增长，这反映出人们对这些天然产物开发新型抗肿瘤药物的兴趣日益浓厚。在研究最多的具有抗癌特性的PTs中，有齐墩果烷型、乌苏烷型和木栓烷型，包括齐墩果酸、甘草次酸、熊果酸、积雪草苷酸以及雷公藤红素等。该领域的广泛研究表明，PTs的抗癌作用是由多种机制介导的，因为它们可调节多种参与癌细胞增殖和存活的分子靶点及信号通路。鉴于这类化合物的抗癌潜力，人们合成了许多半合成衍生物，旨在提高其治疗活性和药代动力学性质，并降低其毒性。与母体化合物相比，其中一些新的半合成衍生物在各种癌细胞系和动物模型中显示出更好的抗癌活性。此外，其中一些化合物已在临床试验中进行了评估，证明对人体使用是安全的。本综述更新了关于具有抗癌活性的齐墩果烷型、乌苏烷型和醌甲基木栓烷型PTs半合成衍生物的最新研究结果。简要介绍了PTs及其抗癌活性，并对2012年至2017年初进行的主要半合成修饰进行了综述和讨论。
