Toropov Andrey A, Benfenati Emilio
Laboratory of Environmental Chemistry and Toxicology, Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, 20157 Milan, Italy.
Bioorg Med Chem. 2006 Jun 1;14(11):3923-8. doi: 10.1016/j.bmc.2006.01.038. Epub 2006 Feb 3.
In the rainbow trout (Oncorhynchus mykiss), we studied the acute toxicity LC(50)-96 h of 274 organic pesticides with a wide variety of molecular structures. Optimization of correlation weights of local and global graph invariants (OCWLGI) gave quantitative structure-activity relationships (QSARs) for predicting toxicity. We used a labeled hydrogen-filled graph (LHFG) to elucidate the molecular structure. We also used the extended connectivity of zero ((0)EC(k)), first ((1)EC(k)), and second ((2)EC(k)) order, numbers of path lengths 2 (P2(k)) and 3 (P3(k)) starting from a given vertex in the LHFG, and valence shells of second order (S2(k)). S2(k) is the sum of the degree of vertices at distance 2 from a given vertex k. The presence of three-, five-, and six-member cycles and hydrogen bond indices suggested they might be used as global LHFG invariants. We applied this method to a broad set of pesticides, to predict toxicity for the trout. The best model used weighted S2(k) and global LHFG invariants. Statistical characteristics of this model are as follows: n=233, r(2)=0.7689, r(2)(pred)=0.7688, s=0.75, F=769 (training set); n=41, r(2)=0.6421, r(2)(pred)=0.4241, s=1.14, F=70 (test set).
在虹鳟鱼（Oncorhynchus mykiss）中，我们研究了274种具有多种分子结构的有机农药的96小时急性毒性半数致死浓度（LC(50)）。局部和全局图不变量相关权重的优化（OCWLGI）给出了用于预测毒性的定量构效关系（QSARs）。我们使用带标记氢填充图（LHFG）来阐明分子结构。我们还使用了零阶（(0)EC(k)）、一阶（(1)EC(k)）和二阶（(2)EC(k)）的扩展连接性、从LHFG中给定顶点出发的路径长度为2（P2(k)）和3（P3(k)）的数量，以及二阶价层（S2(k)）。S2(k)是与给定顶点k距离为2的顶点度数之和。三元、五元及六元环的存在和氢键指数表明它们可能被用作全局LHFG不变量。我们将此方法应用于广泛的农药组，以预测对虹鳟鱼的毒性。最佳模型使用了加权S2(k)和全局LHFG不变量。该模型的统计特征如下：n = 233，r(2) = 0.7689，r(2)(pred) = 0.7688，s = 0.75，F = 769（训练集）；n = 41，r(2) = 0.6421，r(2)(pred) = 0.4241，s = 1.14，F = 70（测试集）。
