Silakari Pratigya, Shrivastava Savitri Devi, Silakari Gyati, Kohli Dharm Veer, Rambabu Gundla, Srivastava Soumya, Shrivastava Santosh Kumar, Silakari Om
Department of Chemistry, Dr HS Gour University, Madhya Pradesh, India.
Eur J Med Chem. 2008 Jul;43(7):1559-69. doi: 10.1016/j.ejmech.2007.09.028. Epub 2007 Oct 11.
Quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for COX-2 enzyme-ligand interaction. QSAR model derived from Hansch analysis demonstrated that COX-2 inhibitory activity is correlated with sum of atomic polarizability (Apol), number of hydrogen-bond donor groups (HBD), energy of the highest occupied molecular orbital (HOMO), desolvation free energy for water (F(H(2)O)) and fraction of areas of molecular shadow in the XY and ZX planes over area of enclosing rectangle (Sxyf and Sxzf) with r ranges 0.870-0.904. The best model was obtained from RSA model having r = 0.940 with good predictive ability (predicted compounds in training set and test set within +/- 1.0 unit of pIC(50)) and can be used in designing better selective COX-2 inhibitors among the congeners in future.
对一系列1,3 - 二芳基 - 4,5,6,7 - 四氢 - 2H - 异吲哚进行了定量构效关系（QSAR）分析，以研究其对环氧合酶 - 2（COX - 2）的抑制作用。QSAR研究基于Hansch的超热力学多参数方法和受体表面分析（RSA）。QSAR研究表明，空间和静电相互作用是COX - 2酶 - 配体相互作用的主要原因。源自Hansch分析的QSAR模型表明，COX - 2抑制活性与原子极化率总和（Apol）、氢键供体基团数量（HBD）、最高占据分子轨道能量（HOMO）、水的去溶剂化自由能（F(H₂O)）以及分子在XY和ZX平面上的阴影面积占包围矩形面积的分数（Sxyf和Sxzf）相关，r范围为0.870 - 0.904。最佳模型来自RSA模型，r = 0.940，具有良好的预测能力（训练集和测试集中预测的化合物pIC₅₀在±1.0单位范围内），可用于未来在同系物中设计更好的选择性COX - 2抑制剂。
