Berger B J, Fairlamb A H
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, United Kingdom.
Antimicrob Agents Chemother. 1994 Jun;38(6):1298-302. doi: 10.1128/AAC.38.6.1298.
The antitrypanosomal drug melarsamine hydrochloride (MelCy) (trade name, Cymelarsan) is a melamino-phenylarsine made by conjugation of one equivalent of melarsen oxide and two equivalents of cysteamine. Immediately after it was dissolved in water, the compound was found to exist as an equilibrium mixture containing MelCy (43%), MelCy which had lost one cysteamine moiety (MelCy -1; 24%), melarsen oxide (33%), and free cysteamine. Small amounts (< 1%) of the oxidation products derived from the last two components were also formed (cystamine and sodium melarsen). On incubation at room temperature, the MelCy content decreased steadily, with an associated increase in the melarsen oxide and sodium melarsen contents. After 5 days in solution at room temperature, 27% of the arsenical agent was MelCy, 14% was MelCy -1, 42% was melarsen oxide, and 17% was sodium melarsen. Since H2O2 production was detectable in MelCy or cysteamine solutions and the addition of small amounts of exogenous H2O2 readily converted the trivalent melarsen oxide to the pentavalent sodium melarsen, it is hypothesized that the nonenzymatic conversion of cysteamine to cystamine produced H2O2, which then oxidized melarsen oxide to sodium melarsen. Similar time course experiments showed that melarsonyl potassium and melarsoprol were more stable in solution.
抗锥虫药盐酸美拉胂胺（MelCy）（商品名， Cymelarsan）是一种通过一当量的美拉胂氧化物与两当量的半胱胺结合而成的美拉米诺 - 苯胂。该化合物溶于水后，立即发现它以一种平衡混合物的形式存在，其中含有MelCy（43%）、失去一个半胱胺部分的MelCy（MelCy -1；24%）、美拉胂氧化物（33%）和游离半胱胺。还形成了少量（<1%）源自最后两种成分的氧化产物（胱胺和美拉胂钠）。在室温下孵育时，MelCy含量稳步下降，同时美拉胂氧化物和美拉胂钠含量相应增加。在室温下溶液中放置5天后，27%的砷剂为MelCy，14%为MelCy -1，42%为美拉胂氧化物，17%为美拉胂钠。由于在MelCy或半胱胺溶液中可检测到过氧化氢的产生，并且添加少量外源性过氧化氢很容易将三价美拉胂氧化物转化为五价美拉胂钠，因此推测半胱胺非酶促转化为胱胺产生了过氧化氢，然后过氧化氢将美拉胂氧化物氧化为美拉胂钠。类似的时间进程实验表明，美拉胂酰钾和美拉索罗在溶液中更稳定。
