In silico rationalization of the structural and physicochemical requirements for photobiological activity in angelicine derivatives and their heteroanalogues

详细信息    查看全文

• 作者：Giordanetto ; Fabrizio ; Fossa ; Paola ; Menozzi ; Giulia ; Mosti ; Luisa
• 关键词：angelicine ; angelicine derivatives ; molecular descriptors ; photobiological activity ; neural networks ; QSAR model
• 刊名：Journal of Computer-Aided Molecular Design
• 出版年：2003
• 出版时间：2003
• 年：2003
• 卷：17
• 期：1
• 页码：53-64
• 全文大小：147 KB

文摘

In PUVA (Psoralen plus UVA) chemotherapy 8-methoxypsoralen is the most widely used compound, although its efficacy is endowed with undesired side effects. In order to have an evident anti-proliferative activity with a reduced phototoxicity, many linear and angular derivatives have been synthesised. In this paper we describe a QSAR study in which, by means of the neural networks methodology, a useful model for predicting biological activity, expressed as ID₅₀ (the UVA dose that reduces to 50% the DNA synthesis in Ehrlich cells), has been derived. A decision tree that is able to discriminate between active and inactive compounds has been built based on recursive partitioning. The study shows the key structural features responsible for the activity and could be a helpful tool in the rational design of new, less toxic, photochemotherapeuthic agents.