Charge transfer and oxy radicals in antimalarial action. Quinones, dapsone metabolites, metal complexes, iminium ions, and peroxides.
A mechanism of action is proposed that encompasses almost all of the main categories of antimalarial agents: quinones and precursors, dapsone metabolites, metal complexes of thiosemicarbazones and biguanides, iminium-type ions from acridines and quinolines, and peroxides. The toxic effect of the drugs is believed to result from the generation of reactive oxygen radicals that usually arise via charge transfer. Electrochemical studies (reduction potential and reversibility) were performed on a number of these agents. Reduction potentials range from -0.23 to -1.52 V. It is likely that the in vivo values are appreciably more positive in certain cases.
D000585:Aminacrine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D003622:Dapsone / Q000494:pharmacology* / Q000627:therapeutic use; D004579:Electron Transport; D005609:Free Radicals; D007097:Imines / Q000494:pharmacology*; D007477:Ions / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy*; D008670:Metals / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology* / Q000627:therapeutic use; D013754:Tetracyclines / Q000494:pharmacology / Q000627:therapeutic use; D013882:Thiosemicarbazones / Q000494:pharmacology
D000634:Aminoquinolines; D001645:Biguanides; D005609:Free Radicals; D007097:Imines; D007477:Ions; D008670:Metals; D010545:Peroxides; D011809:Quinones; D013754:Tetracyclines; D013882:Thiosemicarbazones; D000585:Aminacrine; D003622:Dapsone; D010100:Oxygen