Ligand - based virtual screening procedure for the prediction and the identification of novel β-amyloid aggregation inhibitors using Kohonen maps and Counterpropagation Artificial Neural Networks

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• 作者：Antreas Afantitis ; Georgia Melagraki ; Panayiotis A. Koutentis ; Haralambos Sarimveis ; George Kollias
• 关键词：Alzheimer’ ; s disease ; β ; -Amyloid inhibitors ; Kohonen map ; CP-ANN ; QSAR ; In silico virtual screening
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：46
• 期：2
• 页码：497-508
• 全文大小：675 K

文摘

In this work we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of 62 N-phenylanthranilic acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence.