Research Centre for Medical Genetics, ul. Moskvorechye 1, Moscow115522, Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt 27-1, Moscow 119234, Russia.
Molecules. 2020 Mar 30;25(7):1577. doi: 10.3390/molecules25071577.
Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol). The kinetic chemiluminescence with the 2,2'-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was = 2000 nM min., for Umifenovir = 300 nMmin., = 4 nMmin.. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.
自由基反应在生命系统的生物学功能中起着重要作用。氧化剂和抗氧化剂之间的平衡是细胞和生物体正常动态平衡所必需的。实验工作证明了流感病毒引起的氧化应激以及一些抗病毒药物的毒性作用的作用。因此,抗病毒药物应该具有其抗氧化和促氧化剂活性的特征,因为它会影响其治疗效率。本研究的目的是量化抗病毒药物乌米酚(阿比多尔)的抗氧化能力,并提出其抗氧化作用的机制。使用 2,2'-偶氮双(2-脒基丙烷)二盐酸盐+鲁米诺体系的动力学化学发光来定量乌米酚相对于标准化合物 Trolox 的抗氧化能力。通过计算机模拟,提出了反应方案和速率常数。0.9 μM 乌米酚(口服 200mg 后乌米酚在血液中的最大浓度)的抗氧化能力高达 1.65±0.18 μM Trolox。因此,乌米酚的总抗氧化能力与 Trolox 的抗氧化能力相当。与 Trolox 不同,乌米酚分两个阶段与自由基反应。对于 Trolox,自由基清除速率常数为 = 2000 nM min.,对于乌米酚= 300 nM min.,= 4 nM min.。乌米酚较慢的动力学为其提供了与 Trolox 相比更持久的抗氧化作用。这种现象可以为补偿由病毒病引起的氧化应激和药物的治疗效果做出重大贡献。