a Department of Chemistry, Faculty of Science , University of Kurdistan , Sanandaj , Iran.
SAR QSAR Environ Res. 2019 Jan;30(1):21-38. doi: 10.1080/1062936X.2018.1545695. Epub 2018 Nov 29.
In this study, based on molecular docking analysis and comparative molecular field analysis (CoMFA) modelling of a series of 71 CD38 inhibitors including 4‑amino-8-quinoline carboxamides and 2,4-diamino-8-quinazoline carboxamides, new CD38 inhibitors were designed. The interactions of the molecules with the greatest and the lowest activities with the nicotinamide mononucleotide (NMN) binding site were investigated by molecular docking analysis. A CoMFA model with four partial least squares regression (PLSR) components was developed to predict the CD38 inhibitory activity of the molecules. The r values for the training and test sets were 0.89 and 0.82, respectively. The Q values for leave-one-out cross-validation (LOO-CV) and leave-many-out cross-validation (LMO-CV) tests on the training set were 0.65 and 0.64, respectively. The CoMFA model was validated by calculating several statistical parameters. CoMFA contour maps were interpreted, and structural features that influence the CD38 inhibitory activity of molecules were determined. Finally, seven new CD38 inhibitors with greater activity with respect to the greatest active molecules were designed.
在这项研究中，基于对包括 4-氨基-8-喹啉甲酰胺和 2,4-二氨基-8-喹唑啉甲酰胺在内的 71 种 CD38 抑制剂的一系列分子对接分析和比较分子场分析（CoMFA）建模，设计了新的 CD38 抑制剂。通过分子对接分析研究了分子与具有最大和最小活性的烟酰胺单核苷酸（NMN）结合位点的相互作用。建立了一个包含四个偏最小二乘回归（PLSR）分量的 CoMFA 模型，以预测分子的 CD38 抑制活性。训练集和测试集的 r 值分别为 0.89 和 0.82。在训练集上进行的留一法交叉验证（LOO-CV）和留多法交叉验证（LMO-CV）测试的 Q 值分别为 0.65 和 0.64。通过计算几个统计参数对 CoMFA 模型进行了验证。解释了 CoMFA 等高线图，并确定了影响分子 CD38 抑制活性的结构特征。最后，设计了七个与最活跃分子相比具有更高活性的新型 CD38 抑制剂。
