Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening
文献类型：期刊论文
| 作者 | Weng, Zhiying1,4; Xu, Guowei2; Chen, Dingyuan2 ; Yang, Yaqing1,4; Song, Gao1,4; Shen, Wen3; Zhang, Shuqun2; Wang, LiangLiang2; Yang, Weimin1,4; Zuo, Zhili2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2020-01-15 |
| 卷号 | 30期号:2页码:7 |
| 关键词 | Adenylyl cyclases Homology modeling Consensus scoring Molecular dynamics simulation Virtual screening Biological evaluation |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2019.126823 |
| 通讯作者 | Yang, Weimin(ywmbessie@yeah.net) ; Zuo, Zhili(zuozhili@mail.kib.ac.cn) |
| 英文摘要 | Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combination of homology modeling followed by an in-vitro, and cell-based biological assay have been performed for discovering a class of novel potent and selective isoform adenylyl cyclase type 8 (AC8) agonist. The computer-aided virtual screening was used to identify fourteen virtual cluster compounds as potential hits which were further subjected to rigorous bioassays. A novel hit compound VHC-7 (ethyl 3-(2,4-dichlorobenzyl)-2-oxoindoline-3-carboxylate) was identified as a highly potent selective AC8 agonist with EC50 value of 0.1052 +/- 0.038 mu M. Remarkably, the molecule herein reported can be explored further to discover greater number of hit compounds with better pharmacokinetic properties as well as to serve as a promising novel hit agonist of AC8 for the treatment of various central nervous system disorders and its associated diseases. |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000504873300015 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/70523]  |
| 专题 | 昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室 |
| 通讯作者 | Yang, Weimin; Zuo, Zhili |
| 作者单位 | 1.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 3.Kunming Med Univ, Dept Resp Med, Affiliated Hosp 2, Kunming 650031, Yunnan, Peoples R China 4.Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Weng, Zhiying,Xu, Guowei,Chen, Dingyuan,et al. Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2020,30(2):7. |
| APA | Weng, Zhiying.,Xu, Guowei.,Chen, Dingyuan.,Yang, Yaqing.,Song, Gao.,...&Zuo, Zhili.(2020).Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,30(2),7. |
| MLA | Weng, Zhiying,et al."Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 30.2(2020):7. |
入库方式： OAI收割
来源：昆明植物研究所
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