State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
School of Basic Medical Science, Guizhou Medical University, Guiyang 550004, China.
Int J Mol Sci. 2022 Oct 31;23(21):13291. doi: 10.3390/ijms232113291.
Cancer has been a major health problem in the world in the past decades. It is urgent to develop new, effective and safe drugs for the treatment of cancer. There are many pentacyclic triterpenoids with positive anti-tumor activity and safety in nature. Oleanolic acid (OA), as one of the pentacyclic triterpenoids, also has broad biological activities including liver protection, anti-inflammatory, hypoglycemic, antiviral and anti-tumor. Therefore, to investigate its anti-tumor activity and mechanism, many OA derivatives have been developed. Some derivatives are less toxic to normal hepatocytes, which may be due to the strong liver protection ability of OA. However, the poor water solubility of OA is one of the main reasons for the weak anti-tumor activity. It is reported that some OA derivatives could enhance solubility by chemically linking some hydrophilic groups to improve anti-tumor activity. This review not only summarizes the highly water-soluble OA derivatives that can improve anti-tumor activity reported in recent years, but also introduces their possible anti-tumor mechanisms.
在过去几十年中，癌症一直是全球主要的健康问题。迫切需要开发新的、有效和安全的癌症治疗药物。自然界中有许多具有积极抗肿瘤活性和安全性的五环三萜类化合物。齐墩果酸（OA）作为五环三萜类化合物之一，也具有广泛的生物活性，包括肝脏保护、抗炎、降血糖、抗病毒和抗肿瘤。因此，为了研究其抗肿瘤活性和机制，开发了许多 OA 衍生物。一些衍生物对正常肝细胞的毒性较小，这可能是由于 OA 具有很强的肝脏保护能力。然而，OA 的水溶性差是其抗肿瘤活性较弱的主要原因之一。据报道，通过将一些亲水基团化学连接到 OA 上来提高其溶解度，可以提高其抗肿瘤活性。本综述不仅总结了近年来报道的可提高抗肿瘤活性的高度水溶性 OA 衍生物，还介绍了其可能的抗肿瘤机制。
