Design, synthesis and biological evaluation of novel dihydrobenzodioxine derivatives as HBV capsid protein inhibitors
文献类型：期刊论文
| 作者 | Liu, Linyue1; Li, Chuanju1; Xie, Yong2; Zhang, Lei1; Chen, Yunfu2,4; Jia, Haiyong1,3 |
| 刊名 | BIOORGANIC CHEMISTRY
 |
| 出版日期 | 2022-11-01 |
| 卷号 | 128页码:12 |
| ISSN号 | 0045-2068 |
| 关键词 | HBV Capsid protein inhibitors Pharmacophore hybrid Scaffold hopping HepAD38 cells |
| DOI | 10.1016/j.bioorg.2022.106052 |
| 通讯作者 | Zhang, Lei(leiqdu@foxmail.com) ; Chen, Yunfu(chenyunfu@hec.cn) ; Jia, Haiyong(502378774@163.com) |
| 英文摘要 | Capsid assembly modulators (CAMs) have recently been revealed to be effective in blocking HBV replication. HBV capsid protein inhibitors reduce and ultimately eliminate HBV by inhibiting virus replication and blocking hepatocyte infection. Sulfonamides are synthetic functional groups in development of different kinds of drugs. Sulfonyl benzamide clinical drugs NVR 3-778 and BA-38017 are lead compounds in discovery of antiviral compounds with increased activity and reduced cytotoxicity by drug design strategies including pharmacophore hybrid, bioisosterism and scaffold hopping. In current study, three series of target compounds were synthesized, and their anti-HBV activity was evaluated against HepAD38 cells. Compound 5a (EC50 = 0.50 & PLUSMN; 0.07 & mu;M, CC50 = 48.16 & PLUSMN; 9.15 & mu;M) showed better anti-HBV DNA replication activity than the lead compound BA-38017, and showed good inhibitory effect on the assembly of HBV capsid protein compared with the clinical drug NVR 3778. In addition, preliminary structure-activity relationship (SAR) and molecular docking studies were conducted to explore potential interactions and binding modes between compounds and target proteins, which may help researchers to find more effective anti-HBV drugs. |
| WOS关键词 | PARTITION-COEFFICIENT ; EXPRESSION ; CELLS ; DNA |
| 资助项目 | National Natural Science Foundation of China (NSFC)[81903468] ; National Natural Science Foundation of China (NSFC)[81803343] ; Natural Science Foundation of Shandong Province[ZR2019BH068] ; Natural Science Foundation of Shandong Province[ZR2019QH005] ; Science and Technology Development Project of Shandong Province[2018WS061] ; Science and Technology Support Plan for Youth Innovation in Universities of Shandong Province[2019KJM001] ; Visiting Scholars Program[2021-02] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| WOS记录号 | WOS:001020609300001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306394]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Lei; Chen, Yunfu; Jia, Haiyong |
| 作者单位 | 1.Weifang Med Univ, Sch Pharm, Weifang, Peoples R China 2.Sunshine Lake Pharm Co Ltd, State Key Lab Antiinfect Drug Dev 2015DQ780357, Dongguan 523871, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Sunshine Lake Pharm Co Ltd, Dongguan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Linyue,Li, Chuanju,Xie, Yong,et al. Design, synthesis and biological evaluation of novel dihydrobenzodioxine derivatives as HBV capsid protein inhibitors[J]. BIOORGANIC CHEMISTRY,2022,128:12. |
| APA | Liu, Linyue,Li, Chuanju,Xie, Yong,Zhang, Lei,Chen, Yunfu,&Jia, Haiyong.(2022).Design, synthesis and biological evaluation of novel dihydrobenzodioxine derivatives as HBV capsid protein inhibitors.BIOORGANIC CHEMISTRY,128,12. |
| MLA | Liu, Linyue,et al."Design, synthesis and biological evaluation of novel dihydrobenzodioxine derivatives as HBV capsid protein inhibitors".BIOORGANIC CHEMISTRY 128(2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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