Ding Ye, Ding Chunyong, Ye Na, Liu Zhiqing, Wold Eric A, Chen Haiying, Wild Christopher, Shen Qiang, Zhou Jia
Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.
Eur J Med Chem. 2016 Oct 21;122:102-117. doi: 10.1016/j.ejmech.2016.06.015. Epub 2016 Jun 13.
Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic.
从历史上看，天然产物一直是并将继续是发现各种治疗药物的宝贵来源。冬凌草甲素是一种广泛应用于传统中药的天然二萜类化合物，具有广泛的生物学效应，包括抗癌和抗炎活性。为了进一步提高其效力、水溶性和生物利用度，冬凌草甲素模板成为药物发现的一个令人兴奋的平台，以产生具有独特靶点和增强药物特性的更好候选药物。已经设计并合成了许多冬凌草甲素衍生物（如HAO472），并在鉴定新药物以及针对人类癌症和其他疾病治疗的相关分子机制研究方面取得了重大进展。本综述总结了药物化学领域在探索新型冬凌草甲素类似物作为潜在抗癌治疗药物方面的最新进展，并详细讨论了这类分子开发和推进至临床应用的未来方向。
