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 r² values for the training and test sets were 0.89 and 0.82, respectively. The Q² 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，基于分子对接分析和比较分子场分析（CoMFA）模型，对一系列71种CD38抑制剂进行了建模，包括4-氨基-8-喹啉羧酰胺和2,4-二氨基-8-喹唑啉羧酰胺，开发了新的CD38抑制剂。设计。通过分子对接分析研究了具有最大和最低活性的分子与烟酰胺单核苷酸（NMN）结合位点的相互作用。具有四个偏最小二乘回归（PLSR）组件的CoMFA模型被开发来预测分子的CD38抑制活性。训练集和测试集的r ²值分别为0.89和0.82。在Q ²训练集上的留一法交叉验证（LOO-CV）和留多法交叉验证（LMO-CV）测试的值分别为0.65和0.64。通过计算几个统计参数验证了CoMFA模型。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，设计了七个相对于最大活性分子具有更大活性的新型CD38抑制剂。