Evgeny T Denisov and Taisa G Denisova
A kinetic analysis of intramolecular oxidation reactions of 1 derivatives in combination with the published data on antimalarial activity makes it possible to formulate the following mechanism of action of the peroxide drugs, analogs of compound 1. Under the reaction of the Fe(II) chelates the compound containing the peroxide group is transformed into the alkoxyl radical. This radical isomerizes to the alkyl radical, which further undergoes intramolecular chain oxidation. This oxidation results in polyatomic hydroperoxides, which, in turn, generates radicals in the reaction with Fe(II). The next cascade of radical reactions generates very reactive hydroxyl radicals, whose sources are peroxyl radicals with hydroperoxide fragments and α-dihydroperoxides. The higher the yield of hydroxyl radicals nOH, the more efficient the drug. The dependence of the antimalarial activity of the ith drug IC50(1)M(i)/ IC50(i)M(1) on the yield of radicals HO nOH is nonlin ear (exponential). The compounds with nOH 3 are efficient.
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