Artemisinin DNA Base Interaction Studies in Presence of Fe(II): LC/TOF MS Separation of Reaction Products

Abstract

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF/MS, was used to investigate the reaction of ART with DNA bases. ART-deoxyadenosine and ART-deoxycytidine interactions, were studied in the presence of iron II ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained fairly unchanged at room temperature but grew after incubation at 37 °C. The change in temperature from room temperature to 37 °C was the main driver of adduct formation in these reactions. ART was found to react with Fe(II) ions as observed from several new chromatographic peaks. ART-deoxyadenosine as well as ART-deoxycytidine in the presence of Fe(II) ions resulted in formation of new chromatographic signatures of adducts consisting of DNA bases and ART. It was clear that addition of iron (II) to DNA base-ART mixtures gave rise to new reaction products mediated by a different reaction mechanism. Studies of ART reactions with DNA in vitro is key in elucidating elusive mechanism of this drug.