Niculescu-Duvăz I, Simon Z, Voiculeţ N
Carcinogenesis. 1985 Apr;6(4):479-86. doi: 10.1093/carcin/6.4.479.
Quantitative structure-activity relationships for the reversion of keratinization of hamster tracheal cell organ culture by structurally related retinoids were formulated. Their biological activities (ED50 . M) were correlated with the following parameters: the minimal topological difference (describing the fit of the considered molecules with a possible receptor site) and 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 uninterrupted 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 ED50 exp and ED50 calc 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.
构建了结构相关的类视黄醇对仓鼠气管细胞器官培养物角质化逆转的定量构效关系。它们的生物活性（ED50，单位为M）与以下参数相关：最小拓扑差异（描述所考虑分子与可能受体位点的契合度）和亲脂性常数。为了计算方便，根据分子环状部分、多烯链和末端官能团的结构修饰，将类视黄醇分为三个系列（A、B和C）。计算得到的回归方程表明，环状部分的立体化学特征（对于A系列，方程1，n = 19，r = 0.926，F = 48.19）以及多烯链的连续共轭（对于B系列，方程6，n = 11，r = 0.954，F = 39.39）对生物活性很重要。为了检验为整个化合物集计算的回归方程（方程10，n = 53，r = 0.853，F = 32.11）的预测潜力，用它来计算15种类视黄醇测试系列的ED50。该系列的ED50实验值和计算值之间的相关性为r = 0.916，F = 60.25。讨论了可能参与与类视黄醇相互作用的受体位点的性质。
