Araújo Jocley Queiroz, Carneiro José Walkimar de Mesquita, de Araujo Martha Teixeira, Leite Franco Henrique Andrade, Taranto Alex Gutterres
Programa de Pós-Graduação em Química Orgânica, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, 24020-150, Niterói, RJ, Brazil.
Bioorg Med Chem. 2008 May 1;16(9):5021-9. doi: 10.1016/j.bmc.2008.03.033. Epub 2008 Mar 16.
Malaria is an infectious disease caused by the unicellular parasite Plasmodium sp. Currently, the malaria parasite is becoming resistant to the traditional pharmacological alternatives, which are ineffective. Artemisinin is the most recent advance in the chemotherapy of malaria. Since it has been proven that artemisinin may act on intracellular heme, we have undertaken a systematic study of several interactions and arrangements between artemisinin and heme. Density Functional Theory calculations were employed to calculate interaction energies, electronic states, and geometrical arrangements for the complex between the heme group and artemisinin. The results show that the interaction between the heme group and artemisinin at long distances occurs through a complex where the iron atom of the heme group retains its electronic features, leading to a quintet state as the most stable one. However, for interaction at short distances, due to artemisinin reduction by the heme group, the most stable complex has a septet spin state. These results suggest that a thermodynamically favorable interaction between artemisinin and heme may happen.
疟疾是一种由单细胞寄生虫疟原虫属引起的传染病。目前，疟原虫对传统的药理学替代药物产生了耐药性，这些药物已无效。青蒿素是疟疾化疗领域的最新进展。由于已证明青蒿素可能作用于细胞内的血红素，我们对青蒿素与血红素之间的几种相互作用和排列进行了系统研究。采用密度泛函理论计算来计算血红素基团与青蒿素之间复合物的相互作用能、电子态和几何排列。结果表明，血红素基团与青蒿素在远距离时的相互作用通过一种复合物发生，其中血红素基团的铁原子保留其电子特征，导致五重态成为最稳定的状态。然而，对于近距离相互作用，由于血红素基团使青蒿素还原，最稳定的复合物具有七重态自旋状态。这些结果表明青蒿素与血红素之间可能发生热力学上有利的相互作用。
