E-State Modeling of Fish Toxicity Independent of 3D Structure Information

Abstract

Topological structure methods are used to model fish toxicity against three classes of organic chemicals. The models were obtained independent of 3D structure information. Further, no mechanism of partitioning was assumed, thus avoiding the problems associated with selection of partitioning system for computation of log P. QSAR models were developed for a set of 92 compounds, including phenols, anilines and substituted aromatic hydrocarbons, yielding excellent statistics: r2 = 0.87, s = 0.25 and q2 = 0.85 leave-one-out (LOO), that are better than those reported in the literature. The model is based on molecular connectivity valence chi-1 index [1chiv], the atom type E-State indices for chlorine [ST(-Cl)] and for ether oxygen [ST(-O-)], and the maximum hydrogen E-State atom value in a molecule [Hmax]. Each of the subgroups was also separately well modeled. The model for the full set is validated through use of external validation test sets and ten-fold cross-validation (repeated three times). The quality of the validation statistics supports the claim that the model may be used for estimation of pLC50 values for similar molecules. Detailed structure interpretation is given for the descriptors in the model. These four structure descriptors encode influence of molecular context of groups as well as counts of those groups, in addition to molecular skeletal structure.

QSAR Studies with E-State Index: Predicting Pharmacophore Signals for Estrogen Receptor Binding Affinity of Triphenylacrylonitriles

“…2) explained 81.42% variance with 75.10% cross-validated variance. The model shows the importance of atoms C 6 and C 18 , presence of hydroxyl substitution at C 12 along with the no. of free terminal atoms of the molecules contribute towards major role in binding to the estrogen receptor.…”

“…Topological models directly give structural information to guide design of new molecules 18) and may predict three-dimensional structural parameters, as well.…”

Quantitative Structure–Activity Relationship Study on Fish Toxicity of Substituted Benzenes

“…The fundamentals for an effective prediction of toxicity are the socalled Quantitative Structure -Toxicity Relationships (QSTRs), a discipline which has become rationalized and systematized recently. QSTR methods have been successfully used to predict the toxicity of many compounds, such as the acute toxicity of phenylsulfonyl carboxylates to Vi-brio fischeri [1], modeling of fish toxicity independent of 3D structure information [2]. However, the main problems encountered in the kind of research are the selection of the description of the molecular structure and an effective technique to build vigorous predictive model.…”

Predicting pharmacophore signals for post-coital antifertility activity of 1-trifluoromethyl-1,2,2-triphenylethylene derivatives: a statistical approximation using E-state index

“…17 An attempt has been undertaken to study the electronic character and topological environment of atoms responsible for pharmacophoric foundation of these group of compounds for post-coital antifertility activity using the electrotopological state atom (E-state) index developed by Kier and Hall. 18,19 Topological models directly give structural information to guide design of new molecules 20 and it has been demonstrated to predict 3-D structural parameters, as well. 21 Atom-level parts of molecules are the critical ingredients in meaningful drug-receptor interaction.…”