Hydroxyl Radical as Key Intermediate in Curing Action of Artemisinin and its AnalogsEvgeny T Denisov* and Taisa G Denisova
Institute of Problems of Chemical Physics, RAS, Chernogolovka, Moscow Region, Russia
- *Corresponding Author:
- Evgeny T Denisov
Institute of Problems of Chemical Physics
RAS, Chernogolovka, Moscow Region, Russia
E-mail: [email protected]
Received date: October 20, 2014; Accepted date: December 15, 2014; Published date: December 18, 2014
Citation: Denisov ET, Denisova TG (2014) Hydroxyl Radical as Key Intermediate in Curing Action of Artemisinin and its Analogs. Med chem 4:798-813. doi: 10.4172/2161-0444.1000233
Copyright: © 2014 Denisov ET, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.