Endoperoxide Derivatives from Marine Organisms: 1,2-Dioxanes of the Plakortin Family as Novel Antimalarial Agents
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- 作者：Caterina Fattorusso ; Giuseppe Campiani ; Bruno Catalanotti ; Marco Persico ; Nicoletta Basilico ; Silvia Parapini ; Donatella Taramelli ; Claudio Campagnuolo ; Ernesto Fattorusso ; Adriana Romano ; Orazio Tagli
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：November 30, 2006
- 年：2006
- 卷：49
- 期：24
- 页码：7088 - 7094
- 全文大小：157K
- 年卷期：v.49,no.24(November 30, 2006)
- ISSN：1520-4804
文摘
Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortissimplex, 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 orderto 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 otherstructural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ringconformation, and the absolute configuration of the stereogenic carbons on the 1,2-dioxane ring, when affectingthe bioactive ring conformation.