Methemoglobinemia Caused by 8-Aminoquinoline Drugs: DFT Calculations Suggest an Analogy to H4B鈥檚 Role in Nitric Oxide Synthase

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• 作者：Haining Liu ; Larry A. Walker ; N. P. Dhammika Nanayakkara ; Robert J. Doerksen
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：February 9, 2011
• 年：2011
• 卷：133
• 期：5
• 页码：1172-1175
• 全文大小：717K
• 年卷期：v.133,no.5(February 9, 2011)
• ISSN：1520-5126

文摘

We suggest a possible mechanism of how 8-aminoquinolines (8-AQ鈥檚) cause hemotoxicity by oxidizing hemoglobin to methemoglobin. In our DFT calculations, we found that 5-hydroxyprimaquine is able to donate an electron to O₂ to facilitate its conversion to H₂O₂. 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 H₄B in nitric oxide synthase. Furthermore, our study offers an approach to inform the design of less toxic antimalarial drugs.