ISSN:
1434-193X
Keywords:
Antiprotozoals
;
Artemisinin
;
Trioxanes
;
Heme
;
Structure-activity relationships
;
Drug research
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A clear-cut correlation between antimalarial potency and the alkylative property of synthetic tricyclic trioxanes 5-10 is reported. Thus, trioxanes 5 and 7, substituted at the C-5a angular position by a methyl or a cyano group, proved to be completely devoid of antimalarial activity, and did not alkylate the heme model MnIITPP. In contrast, both the anti-Plasmodium activity and the alkylative property were restored in the C-5a-unsubstituted analog 8, bearing a methoxymethyl group at C-3. Reaction of 8 with MnIITPP furnished the covalent adduct 18, resulting from trapping of the methoxymethyl radical by the heme model. All these results reinforce the hypothesis that the metalloporphyrin closely interacts with the peroxide bond of the drug to bring about activation of these trioxane antimalarial agents.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
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