Galvez-Llompart María, Zanni Riccardo, García-Domenech Ramón
Molecular Connectivity & Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avenida V.A. Estelles s/n, Burjasot, Valencia 46100, Spain.
Int J Mol Sci. 2011;12(12):9481-503. doi: 10.3390/ijms12129481. Epub 2011 Dec 20.
One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds.
当今慢性炎症性疾病治疗中的一个主要药理学问题在于，抗炎药物通常会表现出副作用。天然产物为鉴定生物活性先导化合物并将其开发成治疗炎症性疾病的药物带来了巨大希望。计算机辅助药物设计已被证明是发现新药的非常有用的工具，具体而言，分子拓扑学已成为实现这一目标的良好技术。通过线性判别分析获得的一种拓扑数学模型已被开发用于寻找新的抗炎天然化合物。已使用其余化合物（即未用于构建模型的化合物）进行了外部验证。最后，对天然产物进行了虚拟筛选，有74种化合物显示出实际的抗炎活性。其中，有54种在文献中先前已被描述为具有抗炎作用。这可以被视为模型验证中的一个优势，也强化了分子拓扑学作为发现新的抗炎天然化合物的有效工具的作用。
