Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
J Chem Inf Model. 2011 Aug 22;51(8):1788-94. doi: 10.1021/ci200107b. Epub 2011 Aug 1.
A structural similarity tool was developed and aimed to search for environmentally persistent drugs. The basis for the tool was a selection of so-called anchor molecules and a multidimensional chemical map of drugs. The map was constructed using principal component analysis covering 899 drugs described by 67 diverse calculated chemical descriptors. The anchor molecules (diclofenac, trimethoprim, and carbamazepine) were selected to represent drugs of known environmental concern. In addition 12 chemicals listed by the Stockholm Convention on persistent organic pollutants were used representing typical environmental pollutants. Chemical similarity was quantified by measuring relative Euclidean distances in the five-dimensional chemical map, and more than 100 nearest neighbors (kNNs) were found within a relative distance of less than 10% from each drug anchor. The developed chemical similarity approach not only identified persistent or semipersistent drugs but also a large number of potentially persistent drugs lacking environmental fate data.
开发了一种结构相似性工具，旨在搜索环境持久性药物。该工具的基础是选择了一些所谓的锚定分子和药物的多维化学图谱。该图谱是使用主成分分析构建的，涵盖了 67 种不同计算化学描述符描述的 899 种药物。选择锚定分子（双氯芬酸、甲氧苄啶和卡马西平）来代表已知具有环境关注的药物。此外，还使用了斯德哥尔摩持久性有机污染物公约列出的 12 种化学物质，代表典型的环境污染物。通过在五维化学图谱中测量相对欧几里得距离来量化化学相似性，并且在每个药物锚点的相对距离小于 10%的范围内找到了 100 多个最近邻 (kNN)。所开发的化学相似性方法不仅可以识别持久性或半持久性药物，还可以识别大量缺乏环境命运数据的潜在持久性药物。
