Mechanism of hydroxyl radical induced antimalarial action of hybrid analogues of 10-dihydroartemisinin

作者：Denisov E T^*; Denisova T G

来源：Russian Chemical Bulletin, 2013, 62(12): 2579-2589.

DOI：10.1007/s11172-013-0376-7

• artemisinin
• hybrid compound
• hydroxyl radical
• 10-dihydroartemisinin
• rate constant
• malaria
• intersecting parabolas model
• oxidation
• peroxyl radical

Kinetic schemes of intramolecular oxidation were constructed for ten hybrid analogues of 10-dihydroartemisinin with heteroatom-containing substituents (N, F, Cl). All steps of the kinetic scheme were characterized by the enthalpy of the reaction. The activation energies and rate constants were calculated using the intersecting parabolas model. During intramolecular oxidation of the model compounds, free radicals are generated, and the key role belongs to hydroxyl radicals. The kinetic method was developed, which provides the possibility to differentiate the therapeutic effect of hybrid compounds induced by the hydroxyl radicals alone from that induced in addition by the presence of substituents. Some compounds showed therapeutic effect which exceeds the effect caused by generation of the hydroxyl radicals alone. Several compounds bear substituents, which decrease the action induced by generation of the hydroxyl radicals. Substituents were identified, which made additional contribution to the therapeutic effect of the substance, thus providing the complex action.

• 出版日期2013-12