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Generation of hydroxyl radicals by the intramolecular oxidation of tricyclic artemisinin analogs and their antimalarial activity

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Abstract

The kinetic schemes were constructed for the intramolecular oxidation of four tricyclic artemisinin derivatives differed in number and arrangement of the methyl groups. Each step of the scheme was characterized by the enthalpy. The activation energies and rate constants were calculated by using the intersecting parabolas model. Three of the four tricyclic derivatives were found to undergo intramolecular oxidation, and the hydroperoxide groups formed generate free radicals. Owing to this, the compounds possess antimalarial activity. The fourth compound is not substantially oxidized due to certain specific features of its structure and exhibits no antimalarial activity. The latter correlates with the number of hydroxyl radicals generated by the compound (n OH). The dep endence of the IC50 index on n OH is nonlinear. Three elementary reactions leading to the generation of reactive hydroxyl radicals were identified.

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Authors and Affiliations

  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 prosp. Akad. Semenova, 142432, Chernogolovka, Moscow Region, Russian Federation

    E. T. Denisov & T. G. Denisova

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  1. E. T. Denisov
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  2. T. G. Denisova
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Correspondence to E. T. Denisov.

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Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1831–1839, October, 2010.

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Denisov, E.T., Denisova, T.G. Generation of hydroxyl radicals by the intramolecular oxidation of tricyclic artemisinin analogs and their antimalarial activity. Russ Chem Bull 59, 1881–1889 (2010). https://doi.org/10.1007/s11172-010-0328-4

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  • DOI: https://doi.org/10.1007/s11172-010-0328-4

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