Toxicity CoMFA

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Fig. 5 Example of steric CoMFA contour map results using APO (2-amino-3H-phenoxazin-3-one) for visualization near green area greater toxicity is correlated with more bulky groups and near yellow area with the less bulky group. 

Specific toxicity and/or TMoA Receptor-specific (Q)SARs (comparative molecular field analysis [CoMFA])... 

Perhaps the most popular example of 3D-QSARis the comparative molecular field analysis (CoMFA), developed by Cramer et al. (40), which has elegantly combined the power of 3D molecular modeling and partial least-square (PLS) optimization technique (41, 42) and found wide applications in medicinal chemistry and toxicity analysis (see below). Most of... 

Several CoMFA and CoMSIA studies were performed, both for optimizing selective androgen receptor modulators and for toxicity predictions. An early AR CoMFA model was reported by Waller et al. [118]. It was based on 28 structurally diverse chemicals from which 21 served as training set and yielded a cross-validated q2 value of 0.792. From the seven test compounds six were predicted within one order of magnitude to the experiment, the remaining deviated by 1.8 log units in K, from the experimental value. 

D 3D AD ADME ADMET ANN ARD BCI BCUT BNN C4.5 CART ClogP CoMFA CV Two dimensional Three dimensional Applicability domain Absorption, distribution metabolism, and excretion Absorption, distribution metabolism, excretion, and toxicity Artificial neural network Automatic relevance determination Bernard chemical information Burden, CAS, University of Texas descriptors Bayesian neural network Decision trees using information entropy Classification and regression tree Calculated partition coefficient between octanol and water Comparative molecular field analysis Cross-validation... 

Bohac, M., Loeprecht, B., Damborsky, J. and Schiiiirmann, G. (2002) Impact of orthogonal signal correction (OSC) on the predictive ability of CoMFA models for the dilate toxicity of nitrobenzenes. Quant. Struct. -Act. Relat., 21, 3-11. 

The CoMFA methodology was also used to describe nonlinear lipophilicity-activity relationships, c.g. the inhibitory activities of quaternary alkylbenzyl-dimethylammonium compounds vs. Clostridium welchii (eqs. 206—208) [1025], other antibacterial and hemolytic activities [1026, 1027], and toxic activities of alkanes in mice (eqs. 209-211) [1026] the results of classical QSAR studies (eqs. 206, 207, 209, and 210) [23, 440] were compared with the corresponding CoMFA results (eqs. 208 and 211) [1025-1027] only homologous series of compounds were investigated. 

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