Inhibition mechanism exploration of quinoline derivatives as PDE10A inhibitors by in silico analysis
文献类型：期刊论文
| 作者 | Wu, Qian1; Gao, Qingping2; Guo, Huanmei1; Li, Dan1; Wang, Jinghui3; Gao, Weimin3; Han, Chunxiao3; Li, Yan3; Yang, Ling4 |
| 刊名 | molecular biosystems
 |
| 出版日期 | 2013 |
| 卷号 | 9期号:3页码:386-397 |
| 英文摘要 | as a potential target for the treatment of schizophrenia, the dual camp/cgmp hydrolyzing enzyme pde10a has attracted a significant amount of attention. in the present work, the inhibition mechanism of 116 structurally diverse quinoline derivatives as pde10a inhibitors was explored by 3d-qsar, molecular docking and molecular dynamics (md) simulations. the qsar models based on the training set containing 88 molecules were established by using comparative molecular field analysis (comfa) and comparative molecular similarity indices analysis (comsia). the resultant optimum comsia model showed strong predictability with a q(2) of 0.497, an r-ncv(2) of 0.964 and an r-pre(2) of 0.885. furthermore, there was good consistency between the comsia model, docking and md results. our findings are: (1) bulky substituents at the 8-position and ring d increase the biological activity. (2) the areas around the 14-position and ring d are the electrostatic and hydrophobic sensitive regions. (3) h-bonds, pi-pi stacking interactions and hydrophobic contacts are crucial in determining the binding affinity to pde10a. (4) the six-membered heterocyclic group at ring d, especially a heterobenzene ring, containing the atom as an h-bond acceptor at the 18-position is essential to water-mediated h-bond networks and favorable in enhancing the inhibitory potency. these models and the derived information may help to provide better understanding of the interaction mechanism of pde10a inhibitors and to facilitate lead optimization and novel inhibitors' design. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | biochemistry & molecular biology |
| 研究领域[WOS] | biochemistry & molecular biology |
| 关键词[WOS] | phosphodiesterase 10a inhibitors ; cyclic-nucleotide phosphodiesterases ; striatum-enriched phosphodiesterase ; orally-active pyrazoloquinolines ; molecular similarity indexes ; immunohistochemical localization ; substrate-specificity ; drug development ; field analysis ; schizophrenia |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000314473500007 |
| 公开日期 | 2015-11-10 |
| 源URL | [http://159.226.238.44/handle/321008/137813]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Weifang Univ, Microscale Sci Inst, Weifang 261061, Shandong, Peoples R China 2.Weifang Vocat Coll, Sch Chem Engn, Weifang 261031, Peoples R China 3.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116024, Liaoning, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Grad Sch, Lab Pharmaceut Resource Discovery, Dalian 116023, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Qian,Gao, Qingping,Guo, Huanmei,et al. Inhibition mechanism exploration of quinoline derivatives as PDE10A inhibitors by in silico analysis[J]. molecular biosystems,2013,9(3):386-397. |
| APA | Wu, Qian.,Gao, Qingping.,Guo, Huanmei.,Li, Dan.,Wang, Jinghui.,...&Yang, Ling.(2013).Inhibition mechanism exploration of quinoline derivatives as PDE10A inhibitors by in silico analysis.molecular biosystems,9(3),386-397. |
| MLA | Wu, Qian,et al."Inhibition mechanism exploration of quinoline derivatives as PDE10A inhibitors by in silico analysis".molecular biosystems 9.3(2013):386-397. |
入库方式： OAI收割
来源：大连化学物理研究所
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