QSAR application in chemical carcinogenesis. II. QSAR analysis of a class of carcinogenesis inhibitor: retinoids

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Abstract
Quantitative structure-activity relationships for the reversion of keratinization of hamster traheal cell organ culture by structurally related retinoids were formulated. Their biological activities (ED50.M) were correlated with the following parameters: (i) the minimal topological difference (describing the fit of the considered molecules with a possible receptor site) and (ii) the lipophilicity constants. For computation purposes the retinoids were divided in three series (A,B and C) according to structural modifications in the cyclic moiety of the molecule, in the polienic chain and in the terminal functional group, respectively. The computed regression equations suggested the importance of the stereochemical features of cyclic moiety (for series A,eq.1, n=19,r=0.926,F=48.19) and of the uninterupted conjugation for the polienic chain (for series B,eq.6,n=11,r=0.954,F=39.39) for the biological activity. In order to check the prediction potential of the regression equation computed for the overall set of compounds (eq.10,n=53,r=0.853,F=32.11), it was used to calculate the ED50 for a test series of 15 retinoids. The correlation obtained between ED50exp and ED50calc for this series was r=0.916,F=60.25. The nature of the receptor site possibly involved in the interaction with retinoids was discussed.