Marine endoperoxides as antimalarial lead compounds
Marine endoperoxides as antimalarial lead compounds
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DOI：
10.1007/s11101-010-9197-6
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发表时间：
2010-12-01
影响因子：
7.7
通讯作者：
Taglialatela-Scafati, Orazio
中科院分区：
文献类型：
--
作者：
Fattorusso, Ernesto;Taglialatela-Scafati, Orazio
疟疾是一种由疟原虫属原生动物引起的疾病，是全球健康的主要威胁之一，每年约有 300-5 亿新的临床病例出现，每年有 1-300 万人死亡。近年来登记的死亡病例数量再次增加，可归因于多重耐药疟原虫菌株的扩散，这使得有限的可用药物不再有效。活生物体是公认的潜在生物活性分子来源，其中海洋天然产物正在成为发现新抗疟化合物的最有趣的来源之一。在本文中，我们将报告针对一类海洋代谢物（即含内过氧化物的衍生物）获得的结果。这些分子中的许多具有简单的六元1,2-二氧化环，带有两个或三个不同复杂性的烷基/芳基。它们可以根据两个内过氧化物-含氧碳之一上连接的基团来划分：过氧缩酮衍生物（甲氧基）或非过氧缩酮衍生物（甲基/乙基）。属于这些类别的分子对氯喹抗性菌株表现出纳摩尔范围的体外抗疟活性。多项研究深入了解了这些分子的作用机制，提出了结构变化以优化其抗疟活性。
Malaria, a pathology caused by protozoa belonging to the genus Plasmodium, is one of the major threats to global health, with about 300-500 million new clinical cases occurring every year and 1-3 million annual deaths. The recrudescence in the number of fatal cases registered in recent years can be attributed to the diffusion of multi-drug resistant strains of Plasmodium, which make less effective the limited armamentarium of available drugs. Living organisms are a recognized source of potentially bioactive molecules and, among them, marine natural products are emerging as one of the most interesting sources to be exploited for the discovery of new antimalarial compounds. In this article we will report results obtained for a single class of marine metabolites, namely endoperoxide-containing derivatives. Many of these molecules possess a simple six-membered 1,2-dioxygenated ring bearing two or three alkyl/aryl groups of different complexity. They can be divided according to the group linked at one of the two endoperoxide-oxygen bearing carbons: peroxyketal derivatives (methoxy group) or non-peroxyketal derivatives (methyl/ethyl groups). Molecules belonging to these classes show in vitro antimalarial activity in the nanomolar range on chloroquine-resistant strains. A number of investigations gave insights into the mechanism of action of these molecules, suggesting structural changes to optimize their antimalarial activity.