Roy Amit, Saraf Shailendra
GRY Institute of Pharmacy, Vidya Vihar, Borawan-451228, Dist. Khargone, MP, India.
Biol Pharm Bull. 2006 Feb;29(2):191-201. doi: 10.1248/bpb.29.191.
The search for limonoids started long back when scientists started looking for the factor responsible for bitterness in citrus which has negative impact on citrus fruit and juice industry worldwide. The term limonoids was derived from limonin, the first tetranortriterpenoid obtained from citrus bitter principles. Compounds belonging to this group have exhibited a range of biological activities like insecticidal, insect antifeedant and growth regulating activity on insects as well as antibacterial, antifungal, antimalarial, anticancer, antiviral and a number of other pharmacological activities on humans. Although hundreds of limonoids have been isolated from various plants but, their occurrence in the plant kingdom is confined to only plant families of order Rutales and that too more abundantly in Meliaceae and Rutaceae, and less frequently in Cneoraceae and Harrisonia sp. of Simaroubaceae. Limonoids are highly oxygenated, modified terpenoids with a prototypical structure either containing or derived from a precursor with a 4,4,8-trimethyl-17-furanylsteroid skeleton. All naturally occurring citrus limonoids contain a furan ring attached to the D-ring, at C-17, as well as oxygen containing functional groups at C-3, C-4, C-7, C-16 and C-17. The structural variations of limonoids found in Rutaceae are less than in Meliaceae and are generally limited to the modification of A and B rings, the limonoids of Meliaceae are more complex with very high degree of oxidation and rearrangement exhibited in the parent limonoid structure. To counter the problem of bitterness in citrus juice and products genetic engineering of citrus to maximize the formation of limonoid glucosides for reducing limonoid bitterness is the focus of recent and future research. Regarding the biological activities of limonoids the investigations are to be directed towards detailed characterization, quantification, and designing a simple as well as versatile synthetic route of apparently important limonoids. Extraction methods too should be optimized; evaluation and establishment of pharmaco-dynamic and kinetic principles, and structure activity relationships should be a key goal associated with limonoids so that they can be safely introduced in our arsenal of pharmaceuticals to safeguard the humanity from the wrath of disease and its discomfort.
对柠檬苦素的探索始于很久以前，当时科学家们开始寻找导致柑橘类水果产生苦味的因素，这种苦味对全球柑橘类水果和果汁产业产生负面影响。“柠檬苦素类化合物”一词源于柠檬苦素，它是从柑橘类苦味成分中获得的第一个四环三萜类化合物。属于这一类别的化合物表现出一系列生物活性，如对昆虫的杀虫、拒食和生长调节活性，以及对人类的抗菌、抗真菌、抗疟疾、抗癌、抗病毒和许多其他药理活性。尽管已经从各种植物中分离出数百种柠檬苦素类化合物，但它们在植物界的存在仅限于芸香目植物科，而且在楝科和芸香科中含量更高，在苦木科和苦木科的哈里斯木属中则较少见。柠檬苦素类化合物是高度氧化的、经过修饰的萜类化合物，其原型结构含有或衍生自具有4,4,8-三甲基-17-呋喃基甾体骨架的前体。所有天然存在的柑橘类柠檬苦素类化合物在C-17处都含有一个连接在D环上的呋喃环，以及在C-3、C-4、C-7、C-16和C-17处的含氧官能团。芸香科中发现的柠檬苦素类化合物的结构变异比楝科中的少，并且通常仅限于A环和B环的修饰，楝科的柠檬苦素类化合物更复杂，在母体柠檬苦素类化合物结构中表现出非常高的氧化和重排程度。为了解决柑橘汁和产品中的苦味问题，柑橘的基因工程以最大限度地形成柠檬苦素类糖苷以减少柠檬苦素类苦味是近期和未来研究的重点。关于柠檬苦素类化合物的生物活性，研究应朝着详细表征、定量以及设计重要柠檬苦素类化合物的简单且通用的合成路线的方向进行。提取方法也应优化；药效学和动力学原理的评估和确立以及构效关系应该是与柠檬苦素类化合物相关的关键目标，以便它们能够安全地引入我们的药物库中，保护人类免受疾病的折磨及其带来的不适。
