REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS

The endoperoxides are a new class of antimalarial agents, of which art emisinin (qinghaosu) is the prototype. We have previously shown that a rtemisinin is capable of alkylating proteins in model reactions. In th e present study, we showed that when Plasmodium falciparum-infected er ythrocytes are treated with a radiolabeled antimalarial endoperoxide, either arteether, dihydroartemisinin, or Ro 42-1611 (arteflene), the r adioactivity is largely coverted into a form which can be extracted wi th sodium dodecyl sulfate (SDS). Autoradiograms of SDS-polyacrylamide gels showed that six malarial proteins are radioactively labeled by th e three endoperoxides. This labeling occurs at physiological concentra tions of drug and is not stage nor strain specific. The labeled protei ns were not the most abundant proteins seen on Coomassie-stained gels. No proteins were labeled when uninfected erythrocytes were treated wi th these drugs, nor when infected erythrocytes were treated with the i nactive analog deoxyarteether. Thus, the antimalarial endoperoxides ap pear to react with specific malarial proteins.