In silico rationalization of the structural and physicochemical requirements for photobiological activity in angelicine derivatives and their heteroanalogues
In silico rationalization of the structural and physicochemical requirements for photobiological activity in angelicine derivatives and their heteroanalogues
复制标题
当归碱衍生物及其异类似物光生物活性的结构和物理化学要求的计算机合理化
DOI：
10.1023/a:1024557113083
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
L. Mosti
中科院分区：
文献类型：
--
作者：
F. Giordanetto;P. Fossa;G. Menozzi;L. Mosti
在PUVA(补骨脂素加UVA)化疗中，8-甲氧补骨脂素是最广泛使用的化合物，尽管其疗效被赋予了不受欢迎的副作用。为了在降低光毒性的同时具有明显的抗增殖活性，人们合成了许多线形和角形的衍生物。在本文中，我们描述了一项QSAR研究，在该研究中，通过神经网络方法，推导出了一个有用的预测生物活性的模型，表示为ID50(在Ehrlich细胞中将DNA合成减少到50%的UVA剂量)。基于递归划分，建立了一种能够区分活性化合物和非活性化合物的决策树。这项研究揭示了导致该活性的关键结构特征，并可能成为合理设计新的、毒性较低的光化学治疗药物的有用工具。
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.