Zuurbier K W, Bakkenist A R, Fokkens R H, Nibbering N M, Wever R, Muijsers A O
E.C. Slater Institute for Biochemical Research, University of Amsterdam, The Netherlands.
Biochem Pharmacol. 1990 Oct 15;40(8):1801-8. doi: 10.1016/0006-2952(90)90359-s.
The chlorinating activity of myeloperoxidase, isolated from human polymorphonuclear neutrophils, was inhibited by the non-steroidal anti-inflammatory drug diclofenac (Voltaren). The concentration of diclofenac needed for 50% inhibition was 20 microM, a value comparable with IC50 values found for other drugs. Diclofenac did not react with HOCl nor with H2O2 but was oxidized in the presence of myeloperoxidase and H2O2 to an orange-coloured unstable product. The rate of oxidation was proportional to the enzyme concentration and to the concentration of diclofenac. but independent of the H2O2 concentration. Presumably both Compound I and Compound II, two intermediates formed during the reaction cycle of myeloperoxidase with H2O2 are able to oxidize diclofenac. In these redox reactions, the active short-living Compound I is reduced to Compound II, thereby inhibiting the chlorinating activity of the enzyme. Analysis by Fast Atom Bombardment mass spectrometry showed that in the presence of H2O2 myeloperoxidase oxidizes diclofenac to dihydroxyazobenzene.
从人多形核中性粒细胞中分离出的髓过氧化物酶的氯化活性受到非甾体抗炎药双氯芬酸（扶他林）的抑制。产生50%抑制作用所需的双氯芬酸浓度为20微摩尔，该值与其他药物的半数抑制浓度值相当。双氯芬酸既不与次氯酸反应，也不与过氧化氢反应，但在髓过氧化物酶和过氧化氢存在的情况下被氧化成橙色不稳定产物。氧化速率与酶浓度和双氯芬酸浓度成正比，但与过氧化氢浓度无关。推测在髓过氧化物酶与过氧化氢反应循环中形成的两种中间体，即化合物I和化合物II，都能够氧化双氯芬酸。在这些氧化还原反应中，活性短寿命的化合物I被还原为化合物II，从而抑制了该酶的氯化活性。快速原子轰击质谱分析表明，在过氧化氢存在的情况下，髓过氧化物酶将双氯芬酸氧化为二羟基偶氮苯。
