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

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摘要 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.

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	仝建波
	冯怡
	王天浩
	吴鲁阳

关键词 ： three-dimensional quantitative structure-activity relationship, Topomer CoMFA, HQSAR, 2,5-diketopiperazine derivatives

Abstract：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.

Key words： three-dimensional quantitative structure-activity relationship Topomer CoMFA HQSAR 2,5-diketopiperazine derivatives

收稿日期: 2019-09-20 出版日期: 2020-08-12

基金资助:This project was supported by the National Natural Science Funds of China (21475081), the Natural Science Foundation of Shaanxi Province (2019JM-237), and the Graduate Innovation Fund of Shaanxi University of Science and Technology

通讯作者: jianbotong@aliyun.com E-mail: jianbotong@aliyun.com

引用本文:

仝建波;冯怡;王天浩;吴鲁阳. Topomer CoMFA, HQSAR Studies and Molecular Docking of 2,5-Diketopiperazine Derivatives as Oxytocin Inhibitors[J]. 结构化学, 2020, 39(8): 1385-1394.
TONG Jian-Bo;FENG Yi;WANG Tian-Hao;WU Lu-Yang. Topomer CoMFA, HQSAR Studies and Molecular Docking of 2,5-Diketopiperazine Derivatives as Oxytocin Inhibitors. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2020, 39(8): 1385-1394.

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http://manu30.magtech.com.cn/jghx/CN/ 或 http://manu30.magtech.com.cn/jghx/CN/Y2020/V39/I8/1385

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