Department of Chemistry and Center CERMO-FC, Université du Québec à Montréal, Downtown Branch, P.O. Box 8888, Montréal, QC H3C 3P8, Canada.
Molecules. 2023 Dec 15;28(24):8105. doi: 10.3390/molecules28248105.
Mesalamine, also called 5-ASA (5-aminosalicylic acid), is a largely used anti-inflammatory agent and is a main choice to treat Ulcerative Colitis. This report is aimed to investigate enzymatic processes involved in the oxidation of mesalamine to better understand some of its side-effects. Oxidation with oxygen (catalyzed by ceruloplasmin) or with hydrogen peroxide (catalyzed by peroxidase or hemoglobin) showed that these oxidases, despite their different mechanisms of oxidation, could recognize mesalamine as a substrate and trigger its oxidation to a corresponding quinone-imine. These enzymes were chosen because they may recognize hydroquinone (a -diphenol) as substrate and oxidize it to -benzoquinone and that mesalamine, as a -aminophenol, presents some similarities with hydroquinone. The UV-Vis kinetics, FTIR and H NMR supported the hypothesis of oxidizing mesalamine. Furthermore, mass spectrometry suggested the quinone-imine as reaction product. Without enzymes, the oxidation process was very slow (days and weeks), but it was markedly accelerated with the oxidases, particularly with peroxidase. Cyclic voltammetry supported the hypothesis of the oxidative process and allowed a ranking of susceptibility to oxidizing mesalamine in comparison with other oxidizable drug molecules with related structures. The susceptibility to oxidation was higher for mesalamine, in comparison with Tylenol (acetaminophen) and with aspirin (salicylic acid).
美沙拉嗪，又称 5-ASA（5-氨基水杨酸），是一种广泛使用的抗炎药，是治疗溃疡性结肠炎的主要选择。本报告旨在研究美沙拉嗪氧化过程中涉及的酶促反应，以更好地了解其一些副作用。用氧气（由铜蓝蛋白催化）或过氧化氢（由过氧化物酶或血红蛋白催化）氧化表明，这些氧化酶尽管氧化机制不同，但可以识别美沙拉嗪作为底物，并将其氧化为相应的醌亚胺。选择这些酶是因为它们可能识别氢醌（邻苯二酚）作为底物，并将其氧化为对苯醌，而美沙拉嗪作为邻氨基酚，与氢醌有一些相似之处。紫外可见动力学、FTIR 和 H NMR 支持氧化美沙拉嗪的假设。此外，质谱法提示醌亚胺为反应产物。没有酶时，氧化过程非常缓慢（需要数天或数周），但与氧化酶（特别是过氧化物酶）一起，氧化过程明显加快。循环伏安法支持氧化过程的假设，并允许对美沙拉嗪与其他具有相关结构的可氧化药物分子的氧化敏感性进行排序。与泰诺林（对乙酰氨基酚）和阿司匹林（水杨酸）相比，美沙拉嗪的氧化敏感性更高。
