Quantitative structure activity relationship (QSAR) for toxicity of chlorophenols on L929 cells in vitro

Quantitative structure activity relationship (QSAR) were developed to predict toxicity of chlorophenols by correlating LC50 values with five molecular descriptors, chosen to represent lipophilic, electronic and steric effects: the n-octanol/water partition coefficient (log Kow), the constant of Hammett (∑σ), the acid dissociation constant (pKa), the order valence molecular connectivity index (1χv) and the perimeter of the efficacious section (∑Dg). The results of the regression analysis showed that log Kow and ∑Dg are the dominant (canonical) predictive factors in determining toxicity of chlorophenols to the cells during 24 h exposures, while log Kow was the only dominant predictive factor contributing to toxicity during in 48 h exposures. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to investigate predictive relationships of the cytotoxicity of chlorophenols and develop visual 3D-QSAR models. The CoMFA model, in which the contribution of the electrostatic field to the biological activity was greater than that of the steric field, exhibited both high consistency and predictability (r2 = 0.968, Q2 = 0.891 for 24 h exposure; but the relationship was poorer for the 48 h exposure: r2 = 0.727, Q2 = 0.394). The CoMSIA model used in this study contained three fields: electrostatic, hydrophobic and steric, of which the relative contribution to the biological activity was 0.767:0.225:0.008. In addition, according to the models for 24 h and 48 h. The time-dependent toxicity and potential mechanisms for inhibition of L929 cells was discussed.