LIPE, Higher School of Technology, University Hassan II of Casablanca, B.P 8012 Oasis, Casablanca, Morocco.
Environ Sci Pollut Res Int. 2024 Nov;31(53):62121-62130. doi: 10.1007/s11356-023-28277-3. Epub 2023 Jul 5.
The efficacy of 34 pyrazoline derivatives as carbonic anhydrase inhibitors was studied in silico. The quantum descriptors were calculated by the DFT/B3LYP method using the 6-31G(d) basis; the dataset was randomly divided into training and testing. By altering the compounds in the sets, four models were created, and they were then used to determine the predicted pIC50 values for the six chemicals in the test set. According to the OECD guidelines for QSAR model validation and the Golbraikh and Tropsha's criteria for model approval, each created model was independently validated both internally and externally, along with YRandomization. Model 3 is chosen because it has higher R, R, and Q values (R = 0.79, R = 0.95, Q = 0.64). Only one descriptor has a proportional influence on pIC50 activity, but the other four descriptors have an inverse influence on pIC50 because of the negative contribution coefficient. Given the descriptors of the model, we could propose new molecules with remarkable inhibitory activity.
通过计算密度泛函理论（DFT）/B3LYP 方法下的量子描述符，对 34 种吡唑啉衍生物作为碳酸酐酶抑制剂的功效进行了计算机模拟研究。使用 6-31G(d)基组对数据集进行了随机划分，分为训练集和测试集。通过改变化合物集，创建了四个模型，然后使用它们来确定测试集中六种化学物质的预测 pIC50 值。根据 OECD 定量构效关系模型验证指南和 Golbraikh 和 Tropsha 的模型批准标准，对每个创建的模型进行了内部和外部的独立验证，同时还进行了 Y 随机化验证。选择模型 3，是因为它具有更高的 R、R 和 Q 值（R=0.79，R=0.95，Q=0.64）。只有一个描述符对 pIC50 活性有直接影响，而其他四个描述符对 pIC50 有负向影响，因为它们的贡献系数为负。根据模型的描述符，我们可以提出具有显著抑制活性的新分子。
