Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania.
Research Centre for Pharmaco-Toxicological Evaluation, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq., No. 2, 300041 Timisoara, Romania.
Molecules. 2022 Oct 3;27(19):6552. doi: 10.3390/molecules27196552.
Medicinal plants have been used by humans since ancient times for the treatment of various diseases and currently represent the main source of a variety of phytocompounds, such as triterpenes. Pentacyclic triterpenes have been subjected to numerous studies that have revealed various biological activities, such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and hepatoprotective effects, which can be employed in therapy. However, due to their high lipophilicity, which is considered to exert a significant influence on their bioavailability, their current use is limited. A frequent approach employed to overcome this obstacle is the chemical derivatization of the core structure with different types of moieties including heterocycles, which are considered key elements in medicinal chemistry. The present review aims to summarize the literature published in the last 10 years regarding the derivatives of pentacyclic triterpenes bearing heterocyclic moieties and focuses on the biologically active derivatives as well as their structure-activity relationships. Predominantly, the targeted positions for the derivatization of the triterpene skeleton are C-3 (hydroxyl/oxo group), C-28 (hydroxyl/carboxyl group), and C-30 (allylic group) or the extension of the main scaffold by fusing various heterocycles with the A-ring of the phytocompound. In addition, numerous derivatives also contain linker moieties that connect the triterpenic scaffold with heterocycles; one such linker, the triazole moiety, stands out as a key pharmacophore for its biological effect. All these studies support the hypothesis that triterpenoid conjugates with heterocyclic moieties may represent promising candidates for future clinical trials.
药用植物自古以来就被人类用于治疗各种疾病，目前是各种植物化合物的主要来源，如三萜类化合物。五环三萜类化合物已经进行了大量研究，揭示了各种生物活性，如抗癌、抗糖尿病、抗炎、抗菌和保肝作用，可用于治疗。然而，由于其高亲脂性，被认为对其生物利用度有重大影响，目前的应用受到限制。克服这一障碍的常用方法是用不同类型的取代基对核心结构进行化学衍生化，包括杂环，这些取代基被认为是药物化学中的关键元素。本综述旨在总结过去 10 年关于含有杂环取代基的五环三萜衍生物的文献，并重点介绍具有生物活性的衍生物及其结构-活性关系。主要的衍生化部位是三萜骨架的 C-3（羟基/氧基）、C-28（羟基/羧基）和 C-30（烯丙基）或通过将各种杂环与植物化合物的 A 环融合来扩展主要支架。此外，许多衍生物还含有连接三萜骨架和杂环的连接子部分；其中一个连接子部分，三唑部分，因其生物效应而成为关键的药效团。所有这些研究都支持这样一种假设，即含有杂环取代基的三萜类化合物缀合物可能是未来临床试验的有前途的候选药物。
