3D-QSAR, HQSAR, molecular docking, and new compound design study of 1,3,6-trisubstituted 1,4-diazepan-7-ones as human KLK7 inhibitors

In this study, the structure and activity relationship of 40 human KLK7 inhibitors was explored by three-dimensional quantitative structure –activity relationship (3D-QSAR) and hologram quantitative structure–activity relationship (HQSAR). 3D-QSAR including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis fields (CoMSIA), and Topomer comparative molecular field analysis (Topomer CoMFA). From the data we got, the 3D-QSAR models (CoMFA withq2 = 0.755,r2 = 0.994; CoMSIA withq2 = 0.602,r2 = 0.980; Topomer CoMFA withq2 = 0.644,r2 = 0.929) and the HQSAR model (q2 = 0.717,r2 = 0.950) had a good predictability. Molecular docking was used to reveal the binding mode between the inhibitors and KLK7 protein further. 3D-QSAR, HQSAR, and molecular docking results also provided guidance for discovering new human KLK7 inhibitors. Finally, 13 new compounds were designed as p otential human KLK7 inhibitors, and the predicted activity values showed an effective inhibition on human KLK7.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research