Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones
Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones
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DOI：
10.1016/j.ejmech.2008.01.003
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发表时间：
2008-10-01
影响因子：
6.7
通讯作者：
Emerenciano, Vicente P.
中科院分区：
文献类型：
--
作者：
Fernandes, Mariane B.;Scotti, Marcus T.;Emerenciano, Vicente P.
一些倍半萜内酯（SL）是许多菊科传统药用植物的活性化合物，具有相当大的细胞毒活性。多项体外研究表明，其对源自人类鼻咽癌 (KB) 的细胞具有抑制活性。化学研究表明，细胞毒性活性是由于 SL 的 α,β-不饱和羰基结构与硫醇（例如半胱氨酸）的反应所致。这些研究支持这样的观点，即 SL 通过选择性烷基化生长调节生物大分子（例如控制细胞分裂的关键酶）来抑制肿瘤生长，从而抑制多种细胞功能，从而引导细胞凋亡。在这项研究中，我们研究了一组 55 种不同的倍半萜内酯，以 5 种骨架为代表（22 种germacranolides、6 种榄香烯内酯、2 种 eudesmanolides、16 种 eudesmanolides）。愈创木酚内酯和正衍生物以及 9 种假愈创木酚内酯），就其细胞毒性特性而言。将实验结果和 3D 分子描述符提交给 Kohonen 自组织图 (SOM)，以对细胞毒活性进行分类（训练集）和预测（测试集）。从获得的结果可以得出结论，只有几何描述符显示出令人满意的值。使用 25 个几何描述符训练集后获得的 Kohonen 图显示出非常显着的匹配，主要是在非活性化合物中（类似于 84%）。分析这两个群体，看到的百分比很高（83%）。测试集显示了最高的匹配度，其中 89% 的物质的细胞毒性活性被正确预测。根据这些结果，讨论了整个数据集和不同结构骨架的子集的抑制效力的重要属性。 (C) 2008 Elsevier Masson SAS。版权所有。
Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis.In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity.From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (similar to 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons. (C) 2008 Elsevier Masson SAS. All rights reserved.