Comparative molecular field analysis drug properties

Klebe, G. and Abraham, U. (1993) On the prediction of binding properties of drug molecules by comparative molecular field analysis, foumal of Medicinal Chemistry, 36, 70-80. 

Klebe, G., Abraham, U. On the Prediction of Binding Properties of Drug Molecules by Comparative Molecular Field Analysis. J. Med. Chem. 1993, 36, 70-80. 

The interactions of drugs with their biological counterparts are determined by intermolecular forces, i.e. by hydrophobic, polar, electrostatic, and steric interactions. Quantitative structure-activity relationships (QSAR) derive models which describe the structural dependence of biological activities either by physicochemical parameters (Hansch analysis), by indicator variables encoding different structural features (Free Wilson analysis), or by three-dimensional molecular property profiles of the compounds (comparative molecular field analysis, CoMFA). 

U. Thibaut, G. Folkers, G. Klebe, H. Kubinyi, A. Merz, and D. Rognan, in 3D-QSAR in Drug Design Theory Methods and Applications, H. Kubinyi, Ed., ESCOM, Leiden, 1993, pp. 711-716. Recommendations for CoMFA Studies and 3D QSAR Publications. Y. C. Martin, K.-H. Kim, and C. T. Lin, in Advances in Quantitative Structure-Property Relationships, M. Charton, Ed., JAl Press, Greenwich, CT, 1996, Vol. 1, pp. 1—52. Comparative Molecular Field Analysis CoMFA. 

The mapping of properties to surface features in SPERM can be regarded as a limiting case of the last class of local similarity measures to be discussed here, these being measures that are based upon electrostatic, steric, and hydrophobic fields analogous to those that underlie current approaches to 3D QSAR (see Comparative Molecular Field Analysis (CoMFA) and Quantitative Structure-Activity Relationships in Drug Design). 

A comparative molecular analysis study based on three-dimensional quantum structure-activity relationships was performed by Pajeva and Wiese [159] on 40 phenothiazines and structurally related drugs to predict their MDR modification. More than 350 theoretical models were derived and evaluated using steric, electrostatic and hydrophobic fields alone and in combination. All examined fields were found to contribute to MDR reversing activity, and their hydrophobic fields improved the correlative and predictive power of the models in all cases. The results point out the role of hydropho-bicity as a space-directed molecular property to explain the differences in anti-MDR activity of the drugs under study. 

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