Citation: Xiao-Zhong CHEN, Guang-Ping LI, Yan SHEN, Yong HU, Juan WANG, Yuan-Qiang WANG, Zhi-Hua LIN. Docking and 3D-QSAR Studies on the Imidazo[1, 5-c]pyrimidine Derivative as EED Inhibitors[J]. Chinese Journal of Structural Chemistry, ;2021, 40(6): 689-702. doi: 10.14102/j.cnki.0254–5861.2011–2994 shu

Docking and 3D-QSAR Studies on the Imidazo[1, 5-c]pyrimidine Derivative as EED Inhibitors

Department of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China

Corresponding author: Yuan-Qiang WANG, wangyqnn@cqut.edu.cn Zhi-Hua LIN, zhlin@cqut.edu.cn
Received Date: 25 September 2020
Accepted Date: 10 November 2020

Fund Project: the National Natural Science Foundation of China 81171508

Figures(7)

Embryonic ectoderm development (EED) has become a novel target for cancer treatment. In this study, a series of EED inhibitors was subjected to a three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking. Accordingly, this is the first of such 3D-QSAR studies in a series of EED inhibitors displaying anti-cancer pharmacological profiles. The CoMFA (q² = 0.792, r² = 0.994, r_pred² = 0.74) and CoMSIA (q² = 0.873, r² = 0.994, r_pred² = 0.81) models demonstrated good robustness and predictive ability. Moreover, molecular docking suggested that cation-π, π-π stacking and hydrogen bonding interactions were the main factors affecting the activity of these inhibitors. Five new small molecules were designed based on the CoMFA and CoMSIA contour maps. These molecules were then submitted to further ADME studies, in which the ADME properties of the five designed molecules were found to be within a reasonable range. In view of the corresponding findings, this study may provide theoretical guidance for the rational design of novel EED inhibitors.
- embryonic ectoderm development,
- CoMFA,
- CoMSIA,
- molecular docking
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