Citation: Jian-Bo TONG, Yi FENG, Tian-Hao WANG, Lu-Yang WU. Topomer CoMFA, HQSAR Studies and Molecular Docking of 2,5-Diketopiperazine Derivatives as Oxytocin Inhibitors[J]. Chinese Journal of Structural Chemistry, ;2020, 39(8): 1385-1394. doi: 10.14102/j.cnki.0254–5861.2011–2611 shu

Topomer CoMFA, HQSAR Studies and Molecular Docking of 2,5-Diketopiperazine Derivatives as Oxytocin Inhibitors

Jian-Bo TONG ^{a, b,,} ,
Yi FENG ^{a, b} ,
Tian-Hao WANG ^{a, b} ,
Lu-Yang WU ^{a, b}

a.
College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
b.
Shaanxi Key Laboratory of Chemical Additives for Industry, Xi'an 710021, China

Corresponding author: Jian-Bo TONG, jianbotong@aliyun.com
Received Date: 20 September 2019
Accepted Date: 16 January 2020

Fund Project: the National Natural Science Funds of China 21475081the Natural Science Foundation of Shaanxi Province 2019JM-237

Figures(7)

Topomer comparative molecular field analysis (Topomer CoMFA) and holographic quantitative structure-activity relationship (HQSAR) for 130 2,5-diketopiperazine derivatives were used to build a three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The results show that the models have high predictive ability. For Topomer CoMFA, the cross-validated q² value is 0.710 and the non-cross-validated r² value is 0.834. The most effective HQSAR model shows that the cross-validation q² value is 0.700, the non-cross-validated r² value is 0.815, and the best hologram length value is 353 using connections and bonds as fragment distinctions. 50 highly active 2,5-diketopiperazine derivatives were designed based on the three-dimensional equipotential map and HQSAR color code map. Finally, the molecular docking method was also used to study the interactions of these new molecules by docking the ligands into the diketopiperazine active site, which revealed the likely bioactive conformations. This study showed that there are extensive interactions between the new molecule and Arg156, Arg122 residues in the active site of diketopiperazine. These results provide useful insights for the design of potent of the new 2,5-diketopiperazine derivatives.
- three-dimensional quantitative structure-activity relationship,
- Topomer CoMFA,
- HQSAR,
- 2,5-diketopiperazine derivatives
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