MNDO/d calcualtioins on the interaction betweena rtemisinin and heme

摘要

The antimalarial activity of artemisinin is supposed to be mediated by its interaction with intraparasitic heme leading to free radicals which would be responsible for killing the parasite. The semi-empirical PM3 method was used to calcualte the molecular electrostatic potential of artemisinin. This shows that artemisinin has a wide negative region which extends from the peroxide oxygens O_1 and O_2 to the carboxyl oxygens O_(11) and O_(14). MNDO/d calcualtionis of two complexes between artmisinin and heme, where the Fe(II) ion of heme interacts with either O_1 and O_2 or with O_(11) and O_(14), respectively, indicate that artemisinin interacts with heme preferentially through the peroxide oxygen atoms leading, however, to a complex with low thermodynamic stability.