The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects and increased drug lipophilicity enhance heme aggregation inhibition at lipid/water interfaces.

ABSTRACT: The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6) (1), which is active in vitro against CQ-resistant P. falciparum and in vivo against P. berghei, has been investigated in relation to hemozoin formation and DNA as possible important targets. Complex 1 interacts with heme and inhibits β-hematin formation both in aqueous medium and near water/n-octanol interfaces at pH ~5 to a greater extent than chloroquine diphosphate (CQDP) or other known metal-based antimalarial agents; the higher inhibition activity is probably related to the higher lipophilicity observed for 1 through partition coefficient measurements at low pH, with respect to CQDP. The interactions of complex 1 with DNA were explored using spectrophotometric and fluorimetric titrations, circular dichroism spectroscopy, v

SUBMITTER: Navarro M 

PROVIDER: S-EPMC3038622 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature