Lopez-Shirley K, Zhang F, Gosser D, Scott M, Meshnick S R
City College of New York, New York.
J Lab Clin Med. 1994 Jan;123(1):126-30.
A number of quinones have been shown to be effective antimalarials. In addition some have been shown to have oxidant effects on glucose-6-phosphate dehydrogenase-deficient red cells. To clarify the mechanism of this oxidant effect and to determine whether it is a general property of antimalarial quinones, the effects of five compounds on red cells were studied. Two, 5-hydroxy-6-demethyl pentaquine (5H6DP) and menadione, caused marked methemoglobin production and the insertion of heme into the red-cell membrane. The other three, atovaquone, daphnetin, and menoctone, did not. The insertion of heme into membranes caused diminished deformability, and this might account for the hemolytic effects. Redox potentials of all five compounds were measured. The two quinones that caused heme release, menadione and 5H6DP, had redox potentials of -141 +/- 12 and -97 +/- 25 mV, respectively, which are similar to the reported redox potentials for hemoglobin. The other three quinones had redox potentials that were either significantly higher or lower. Thus only quinones of the appropriate redox potentials are likely to be toxic to red cells.
许多醌类已被证明是有效的抗疟药物。此外，一些醌类已被证明对葡萄糖-6-磷酸脱氢酶缺乏的红细胞具有氧化作用。为了阐明这种氧化作用的机制，并确定它是否是抗疟醌类的普遍特性，研究了五种化合物对红细胞的影响。其中两种，5-羟基-6-去甲基戊喹（5H6DP）和甲萘醌，导致明显的高铁血红蛋白生成以及血红素插入红细胞膜。另外三种，阿托伐醌、瑞香素和甲辛醌，则没有这种作用。血红素插入膜中会导致变形性降低，这可能是溶血作用的原因。测量了所有五种化合物的氧化还原电位。导致血红素释放的两种醌类，甲萘醌和5H6DP，其氧化还原电位分别为-141±12和-97±25 mV，这与报道的血红蛋白氧化还原电位相似。另外三种醌类的氧化还原电位要么显著更高，要么显著更低。因此，只有具有适当氧化还原电位的醌类才可能对红细胞有毒性。
