Manadoperoxides A−D from the Indonesian Sponge Plakortis cfr. simplex. Further Insights on the Structure−Activity Relationships of Simple 1,2-Dioxane Antimalarials

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• 作者：Caterina Fattorusso ; Marco Persico ; Barbara Calcinai ; Carlo Cerrano ; Silvia Parapini ; Donatella Taramelli ; Ettore Novellino ; Adriana Romano ; Fernando Scala ; Ernesto Fattorusso ; Orazio Taglialatela-Scaf
• 刊名：Journal of Natural Products
• 出版年：2010
• 出版时间：June 25, 2010
• 年：2010
• 卷：73
• 期：6
• 页码：1138-1145
• 全文大小：231K
• 年卷期：v.73,no.6(June 25, 2010)
• ISSN：1520-6025

文摘

The new endoperoxyketal polyketides manadoperoxides A−D (2−5) have been isolated from the Indonesian sponge Plakortis cfr. simplex and their stereostructures established by means of spectroscopic data and semisynthetic transformations. Manadoperoxides were assayed in vitro against D10 and W2 strains of Plasmodium falciparum and showed moderate antimalarial activity compared to that of plakortin (1) and peroxyplakoric B₃ ester (9), the latter differing from manadoperoxide B only by minor structural details. This unexpected difference in the antimalarial activity has been rationalized on the basis of our recently published model for the interaction of 1,2-dioxanes with heme and production of C-centered radicals toxic to the parasite. For the manadoperoxides, either the endoperoxide linkage is inaccessible to the heme iron or the O1 radical cannot evolve to produce a C-centered radical.