Structure–Activity Relationships of Synthetic Tricyclic Trioxanes Related to Artemisinin: The Unexpected Alkylative Property of a 3-(Methoxymethyl) Analog
✍ Scribed by Olivier Provot; Boris Camuzat-Dedenis; Mohamed Hamzaoui; Henri Moskowitz; Joëlle Mayrargue; Anne Robert; Jérôme Cazelles; Bernard Meunier; Fatima Zouhiri; Didier Desmaële; Jean d'Angelo; Jacqueline Mahuteau; Frédérick Gay; Liliane Cicéron
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 277 KB
- Volume
- 1999
- Category
- Article
- ISSN
- 1434-193X
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✦ Synopsis
A clear-cut correlation between antimalarial potency and the restored in the C-5a-unsubstituted analog 8, bearing a methoxymethyl group at C-3. Reaction of 8 with Mn II TPP alkylative property of synthetic tricyclic trioxanes 5-10 is reported. Thus, trioxanes 5 and 7, substituted at the C-5a furnished the covalent adduct 18, resulting from trapping of the methoxymethyl radical by the heme model. All these angular position by a methyl or a cyano group, proved to be completely devoid of antimalarial activity, and did not results reinforce the hypothesis that the metalloporphyrin closely interacts with the peroxide bond of the drug to bring alkylate the heme model Mn II TPP. In contrast, both the anti-Plasmodium activity and the alkylative property were about activation of these trioxane antimalarial agents.
oxide moiety, which initially gives rise to oxyl radicals.
ent adduct between radical 4 and an Mn II heme model.