冬凌草甲素抗肿瘤作用机制及其结构改造研究进展

Research Progress in Anti-tumor Mechanism and Structural Modification of Natural Oridonin

天然产物在新药研发中占重要地位,在抗肿瘤药物研究领域,很多活性优良、作用机制和靶点独特的药物都是从活性天然产物中发现的。冬凌草甲素属于ent-贝壳杉烷型二萜化合物,对多种肿瘤具有很好的生长抑制活性。冬凌草甲素的抗肿瘤活性中心为其α,β-不饱和环戊酮结构,其抗肿瘤作用机制涉及细胞凋亡、细胞自噬、细胞周期阻滞等多个方面;近年来,国内外药学工作者针对冬凌草甲素展开了作用机制的深入探索,以及对其提高抗肿瘤活性的结构改造等广泛研究。本文将重点针对这两方面进行综述,期望给药学工作者提供参考。

Natural products play an important role in the development of new drugs. In the long history of developing anticancer drugs, numerous antitumor drugs, which have outstanding anti-proliferation activities, unique mechanisms of action and special targets, are discovered from natural products. Oridonin belongs to ent-type kaurane diterpenoids, and has good activity against a variety of tumors. The activity center of oridonin is α,β-unsaturated cyclopentanone, which can react with Michael donor. The anticancer mechanisms of oridonin include apoptosis, autophagy, cell cycle arrest, and so on. The studies on oridonin,including investigation of the mechanism of action in depth and structural modification to improve the antitumor activity, have been carried out vigorously. This review will summarize these two aspects.