Endoperoxide derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents
Endoperoxide derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents
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DOI：
10.1021/jm060899g
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发表时间：
2006-11-30
影响因子：
7.3
通讯作者：
Taglialatela-Scafati, Orazio
中科院分区：
文献类型：
--
作者：
Fattorusso, Caterina;Campiani, Giuseppe;Taglialatela-Scafati, Orazio
Plakortin (1) 是一种非常简单的 1,2-二恶烷衍生物，从海洋海绵 Plakortis simplex 中提取，对恶性疟原虫的氯喹耐药菌株表现出亚微摩尔活性。使用 Plakortin 作为新型抗疟药物，我们制备了一系列半合成衍生物，以便深入了解简单 1,2-二恶烷表现出抗疟活性的结构要求。本文报道了它们的合成、光谱和计算分析以及体外抗疟活性。获得的结果除了证实了环过氧化物官能团的关键作用外，还揭示了对于抗疟活性至关重要的其他结构特征，即“西方”烷基侧链、二恶烷环构象以及1,2-二恶烷环上立体碳的绝对构型（当影响生物活性环构象时）。
Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortis simplex, showing a submicromolar activity against chloroquine-resistant strains of Plasmodium falciparum. Using plakortin as a novel antimalarial hit, we have prepared a series of semisynthetic derivatives in order to gain insights into the structural requirements of simple 1,2-dioxanes for exhibiting antimalarial activity. Their synthesis, spectroscopic and computational analysis, and in vitro antimalarial activity are herein reported. Results obtained, besides confirming the crucial role of the cycloperoxide functionality, revealed other structural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ring conformation, and the absolute configuration of the stereogenic carbons on the 1,2-dioxane ring, when affecting the bioactive ring conformation.