8-氨基喹啉类药物导致的高铁血红蛋白血症：DFT 计算提示其与 H4B 在一氧化氮合酶中的作用类似。
Methemoglobinemia caused by 8-aminoquinoline drugs: DFT calculations suggest an analogy to H4B's role in nitric oxide synthase.
机构信息
Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, Mississippi 38677, United States.
出版信息
J Am Chem Soc. 2011 Feb 9;133(5):1172-5. doi: 10.1021/ja107472c. Epub 2011 Jan 18.
Abstract
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(2)O(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(4)B in nitric oxide synthase. Furthermore, our study offers an approach to inform the design of less toxic antimalarial drugs.
摘要
我们提出了 8-氨基喹啉（8-AQ）类药物通过氧化血红蛋白形成高铁血红蛋白从而导致血液毒性的可能机制。在我们的密度泛函理论（DFT）计算中，我们发现 5-羟基伯喹能够向 O(2) 提供一个电子，从而促进其转化为 H(2)O(2)。与此同时，Fe(II)被氧化为 Fe(III)，形成高铁血红蛋白。在这个机制中，8-AQ 类药物发挥了类似于一氧化氮合酶中 H(4)B 的作用。此外，我们的研究为设计毒性更低的抗疟药物提供了一种方法。
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2
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Chem Rev. 2010 Feb 10;110(2):949-1017. doi: 10.1021/cr900121s.
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