Department of Chemistry and Physics, Augusta University, Augusta, GA 30912, USA.
Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA.
Molecules. 2022 Dec 16;27(24):8981. doi: 10.3390/molecules27248981.
Ursolic acid (UA) is a pentacyclic triterpene isolated from a large variety of vegetables, fruits and many traditional medicinal plants. It is a structural isomer of Oleanolic Acid. The medicinal application of UA has been explored extensively over the last two decades. The diverse pharmacological properties of UA include anti-inflammatory, antimicrobial, antiviral, antioxidant, anti-proliferative, etc. Especially, UA holds a promising position, potentially, as a cancer preventive and therapeutic agent due to its relatively non-toxic properties against normal cells but its antioxidant and antiproliferative activities against cancer cells. Cell culture studies have shown interference of UA with multiple pharmacological and molecular targets that play a critical role in many cells signaling pathways. Although UA is considered a privileged natural product, its clinical applications are limited due to its low absorption through the gastro-intestinal track and rapid elimination. The low bioavailability of UA limits its use as a therapeutic drug. To overcome these drawbacks and utilize the importance of the scaffold, many researchers have been engaged in designing and developing synthetic analogs of UA via structural modifications. This present review summarizes the synthetic UA analogs and their cytotoxic antiproliferative properties reported in the last two decades.
熊果酸(UA)是一种五环三萜,从各种蔬菜、水果和许多传统药用植物中分离得到。它是齐墩果酸的结构异构体。在过去的二十年中,UA 的药用应用已经得到了广泛的探索。UA 的多种药理学特性包括抗炎、抗菌、抗病毒、抗氧化、抗增殖等。特别是,UA 因其对正常细胞的相对无毒特性,但对癌细胞的抗氧化和抗增殖活性,有望成为一种癌症预防和治疗药物。细胞培养研究表明,UA 干扰了在许多细胞信号通路中起关键作用的多种药理学和分子靶标。尽管 UA 被认为是一种特权天然产物,但由于其在胃肠道中的低吸收率和快速消除,其临床应用受到限制。UA 的生物利用度低限制了其作为治疗药物的使用。为了克服这些缺点并利用支架的重要性,许多研究人员通过结构修饰设计和开发了 UA 的合成类似物。本综述总结了过去二十年中报道的合成 UA 类似物及其细胞毒性抗增殖特性。