用于抗高血糖先导物开发的钠葡萄糖协同转运蛋白2（SGLT2）抑制剂的定量构效关系分析
QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development.
作者信息
Gandhi A, Masand V, Zaki M E A, Al-Hussain S A, Ghorbal A Ben, Chapolikar A
机构信息
Department of Chemistry, Government College of Arts and Science, Aurangabad, Maharashtra, India.
Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati, Maharashtra, India.
出版信息
SAR QSAR Environ Res. 2021 Sep;32(9):731-744. doi: 10.1080/1062936X.2021.1971295.
QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 Å from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with = 0.83, = 51.54, = 0.79, = 0.79, = 0.88, F = 0.76-0.81, = 0.77, = 0.85, and with RMSE < RMSE was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.
对90种钠依赖性葡萄糖协同转运蛋白2（SGLT2）抑制剂的数据集进行了定量构效关系（QSAR）建模。定量和解释性评估揭示了一些导致这些化合物对SGLT2具有抑制效力的细微且独特的结构特征，例如分子中距亲脂性原子8 Å处的环碳原子数量尽可能少（fringClipo8A）以及供体原子七个键内存在的亲脂性原子部分电荷总和的可能值更大（lipo_don_7Bc）。多变量遗传算法-多元线性回归（GA-MLR）和全面的验证方法得出了一个统计稳健的QSAR模型，各种统计参数显示出其具有非常高的预测能力。提出了一个QSAR模型，其R² = 0.83，r² = 51.54，Q²LOO = 0.79，Q²LMO = 0.79，Q²EXT = 0.88，F = 0.76 - 0.81，r²adj = 0.77，r²pred = 0.85，且RMSE < RMSE。该QSAR模型将有助于合成化学家开发作为抗糖尿病先导物的SGLT2抑制剂。
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