Hasdenteufel Frederic, Luyasu Samuel, Hougardy Nicolas, Fisher Malcolm, Boisbrun Michel, Mertes Paul-Michel, Kanny Gisele
Allergy Diseases: Diagnosis and Therapeutics, Department of Internal Medicine, Clinical Immunology and Allergology, University Hospital of Nancy, Nancy Cedex, France.
Curr Clin Pharmacol. 2012 Feb 1;7(1):15-27. doi: 10.2174/157488412799218815.
Structure-activity relationships (SARs) refer to the relation between chemical structure and pharmacologic activity for a series of compounds. Since the pioneering work of Crum-Brown and Fraser in 1868, they have been increasingly used in the pharmaceutical, chemical and cosmetic industries, especially for drug and chemical design purposes. Structure-activity relationships may be based on various techniques, ranging from considerations of similarity or diversity of molecules to mathematical relationships linking chemical structures to measured activities, the latter being referred to as quantitative SAR or QSAR. This review aims at briefly reviewing the history of SARs and highlighting their interest in delayed and immediate drug allergy using selected examples from the literature. Studies of SAR are commonly conducted in the area of contact dermatitis, a delayed hypersensitivity reaction, to determine the allergenic potential of a given compound without animal testing. In immediate, immunoglobulin E-mediated drug hypersensitivity, this kind of approach remains rather confidential. It has been mainly applied to neuromuscular blocking drugs (muscle relaxants) and betalactam antibiotics (penicillins, cephalosporins). This review shows that SARs can prove useful to (i) predict the allergenic potential of a chemical or a drug, (ii) help identify putative antigenic determinants for each patient or small group of patients sharing the same cross-reactivity pattern, and (iii) predict the likelihood of adverse reactions to related molecules and select safe alternatives.
构效关系（SARs）是指一系列化合物的化学结构与药理活性之间的关系。自1868年克拉姆 - 布朗和弗雷泽的开创性工作以来，它们在制药、化工和化妆品行业的应用越来越广泛，特别是用于药物和化学设计目的。构效关系可能基于各种技术，从分子相似性或多样性的考虑到将化学结构与测量活性联系起来的数学关系，后者被称为定量构效关系或QSAR。本综述旨在简要回顾构效关系的历史，并通过文献中的实例突出其在迟发性和速发型药物过敏中的意义。构效关系的研究通常在接触性皮炎领域进行，这是一种迟发性超敏反应，用于在不进行动物试验的情况下确定给定化合物的致敏潜力。在速发型、免疫球蛋白E介导的药物超敏反应中，这种方法仍然相当保密。它主要应用于神经肌肉阻滞药物（肌肉松弛剂）和β-内酰胺抗生素（青霉素、头孢菌素）。本综述表明，构效关系有助于（i）预测化学物质或药物的致敏潜力，（ii）帮助识别每个患者或具有相同交叉反应模式的一小群患者的推定抗原决定簇，以及（iii）预测对相关分子不良反应的可能性并选择安全的替代物。
