Methemoglobinemia Caused by 8-Aminoquinoline Drugs: DFT Calculations Suggest an Analogy to H_4B's Role in Nitric Oxide Synthase

摘要

We suggest a possible mechanism of how 8-aminoquinolines (8-AQ's) cause hemotoxicity by oxidizing hemoglobin to methemoglobin. In our DFT calculations, we found that 5-hydroxyprimaquine is able to donate an electron to O_2 to facilitate its conversion to H_2O_2. Meanwhile, Fe(II) is oxidized to Fe(III) and methemoglobin is formed. In this mechanism, the 8-AQ drug plays a similar role as that of H_4B in nitric oxide synthase. Furthermore, our study offers an approach to inform the design of less toxic antimalarial drugs.