苯甲酸衍生物对酪氨酸酶活力抑制的定量构效关系

Studies on quantitative structure-activity-relationship inhibitory effects of benzoic acid derivatives on tyrosinase

利用Gaussian 03W程序,采用密度泛函理论(DFT)的B3LYP/6-31G^(**)方法全优化计算,计算25种苯甲酸衍生物的量子化学参数。通过相关性分析,从8种量化参数中选4种影响化合物活性的独立参数,然后利用多元线性逐步回归法,研究4种参数对酪氨酸酶抑制活性(log(1/IC_(50)))的关系,建立QSAR方程,结果表明,该类化合物的分子以最高占据轨道能(E_(HOMO)),分子中的最大负电荷(Q_(max)^-)以及疏水性参数(ClogP)对抑制剂活性(log(1/IC_(50)))影响最大,其结果为进一步研究酪氨酸酶抑制剂的设计提供参考。

The quantum chemical parameters of 25 kinds of benzoic acid derivatives had been calculated using Gaussian03W package of programs at the DFT/B3LYP of level theory, with the 6-31G^＊＊ basis set. Via correlation analysis, four main independent factors affecting the activity of the compounds were selected out from the eight chemical parameters. The relationship between four chemical parameters and tyrosinase inhibitory activity （ log （ 1/IC50 ） ） was studied, and then, the QSAR equation was established by using a stepwise multiple linear regression method. The results showed that, the energy of the LUMO, the maximum negative charges and the molecular hydrophobicity （ClogP） have the most significant contributions to the inhibitory activity of the compounds. Moreover, the results provided a theoretical foundation for synthesizing new inhibitory agents.