Citation: Zeng Qiaoling, Liu Yingxiang, Li Geng, Ma Yuzhuo. Studies on Molecular Docking and QSAR of Dihydropyrimido[4, 5-d] pyrimidine Derivatives as CSF-1R Inhibitors[J]. Chemistry, ;2019, 82(10): 917-925. shu

Studies on Molecular Docking and QSAR of Dihydropyrimido[4, 5-d] pyrimidine Derivatives as CSF-1R Inhibitors

1.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006
2.
College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006

Received Date: 30 June 2019
Accepted Date: 13 August 2019

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Colony stimulating factor 1 receptor (CSF-1R) is a member of the type Ⅲ receptor tyrosine kinase family, which plays a crucial role in the regulation of the monocyte/macrophage system. Abnormal expression of CSF-1R and its ligands is closely related to tumor progression. Therefore, CSF-1R signaling might be an effective target for anti-cancer therapy. In this study, the three-dimensional quantitative structure-activity relationship (3D-QSAR) models were generated for 54 dihydropyrimido[4, 5-d]pyrimidine CSF-1R inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The cross-validation coefficient (q²) of the CoMFA model and CoMSIA model were 0.725 and 0.636, and the fitting verification coefficients (r²) were 0.960 and 0.958. The results showed that both models have good predictive ability. The contour maps of the models could visually reflect the effect of different substituents on the activity, and the stereo field and the hydrophobic field contributed more to the activity. The molecular docking study showed that the amino acid residue Cys666 and Asp796 play a role in the ligand-receptor binding process, and the molecular docking binding mode is consistent with the results obtained by 3D-QSAR. The information could provide a theoretical basis for further optimization of this class CSF-1R inhibitors.
- CSF-1R,
- Molecular docking,
- 3D-QSAR model,
- Dihydropyrimido[4, 5-d] pyrimidine derivatives
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1.
沈阳化工大学材料科学与工程学院沈阳 110142