99. “Epiartemisinin, a Remarkably Poor Antimalarial: Implications for the Mode of Action”
    Jefford, C. W.; Burger, U.; Millasson-Schmidt, P.; Bernardinelli, G.; Robinson, B. L.; Peters, W.
    Helv. Chim. Acta 2000, 83, 1239-1246.

Epiartemisinin (7) was prepared by the base epimerization of artemisinin (1) and its structure determined by X-ray analysis. The antimalarial activity of 7 against the chloroquine-sensitive and resistant strains of Plasmodium berghei and P. yoelii in the mouse was compared with that of the highly effective schizonticide 1 and found to be drastically diminished. It is argued that the mode of action on the intraerythrocytic parasite by 7 is compromised by steric hindrance arising from the α-disposed Me group. In the initial step, intimate complexation with heme is hindered or biased to favor the formation of a less potent C-centered radical, the final lethal agent.

DOI : 10.1002/1522-2675(20000607)83:6<1239::AID-HLCA1239>3.0.CO;2-S 

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