Usnic acid is a lichen compound which is extensively studied due to its cytotoxic, antiproliferative, antimicrobial, antiviral, antiprotozoal, and anti-inflammatory activities. Despite a broad spectrum of biological properties, usnic acid is a hepatotoxic agent, thus its potential use as a drug is limited. Certain hepatotoxic drugs may act by generating reactive metabolites that damage the liver. The aim of the study was to predict the biotransformation of usnic acid enantiomers to reactive products using a trapping assay with glutathione in human, rat, and mice liver microsomes. Our results indicate that each enantiomer forms two reactive metabolites; in turn, these metabolites form adducts with glutathione, which may partially explain the toxicity of usnic acid. In silico analysis indicated structural alerts for the generation of reactive metabolites in usnic acid formula. This study proposes a novel mode of the hepatic toxicity of usnic acid enantiomers; it also provides some useful suggestions for designing safer usnic acid derivatives.

松萝酸是一种地衣化合物，由于其细胞毒性，抗增殖，抗微生物，抗病毒，抗原生动物和抗炎活性而被广泛研究。尽管具有广泛的生物学特性，松萝酸还是一种肝毒性剂，因此其潜在的药物用途受到了限制。某些肝毒性药物可能通过产生损害肝脏的反应性代谢物来发挥作用。该研究的目的是在人，大鼠和小鼠的肝微粒体中使用谷胱甘肽进行捕获分析，预测松香酸对映异构体向反应产物的生物转化。我们的结果表明，每个对映异构体均形成两个反应性代谢物；反过来，这些代谢物与谷胱甘肽形成加合物，这可能部分解释了松萝酸的毒性。计算机分析表明在松萝酸配方中反应性代谢产物的产生产生了结构性警报。这项研究提出了松香酸对映异构体的肝毒性的一种新模式。它还为设计更安全的松萝酸衍生物提供了一些有用的建议。