Iron(II)-induced degradation of antimalarial beta-sulfonyl endoperoxides: evidence for the generation of potentially cytotoxic carbocations.

Szpilman, A M; Korshin, E E; Hoos, R; Posner, G H; Bachi, M D

Szpilman, A M; Korshin, E E; Hoos, R; Posner, G H; Bachi, M D.

Afiliación

Szpilman AM; Department of Organic Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.

J Org Chem ; 66(20): 6531-40, 2001 Oct 05.

Article en En | MEDLINE | ID: mdl-11578201

RESUMEN

Reactions of antimalarial beta-sulfonyl endoperoxides 9 and 10, which, like yingzhaosu A (2), derive from the 2,3-dioxabicyclo[3.3.1]nonane system 3, with iron(II) salts were studied. Product analysis of the iron(II)-induced degradations provided evidence for the intermediacy of carbon-centered cyclohexyl radicals 20 and 31 and their possible oxidation to the corresponding carbocations 21 and 32. It is conceivable that the antimalarial activity of beta-sulfonyl endoperoxides of type 5 may derive from alkylation of vital intraparasitic biomolecules by free radicals and/or carbocations, generated within the malaria parasite through a similar iron(II)-induced degradation process.

Asunto(s)

Antimaláricos/metabolismo; Hierro/farmacología; Peróxidos/metabolismo; Antimaláricos/química; Radicales Libres/química; Radicales Libres/metabolismo; Oxidación-Reducción; Peróxidos/química; Peróxidos/uso terapéutico; Profármacos/química; Profármacos/metabolismo; Ácidos Sulfínicos/química

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peróxidos / Hierro / Antimaláricos Idioma: En Revista: J Org Chem Año: 2001 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos

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