Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction
文献类型：期刊论文
| 作者 | Zhang, Feng-Hua1; Debnath, Bikash3; Xu, Zhong-Liang1; Yang, Liu-Meng2; Song, Li-Rui1; Zheng, Yong-Tang2; Neamati, Nouri3; Long, Ya-Qiu1 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-01-05 |
| 卷号 | 125页码:1051-1063 |
| 关键词 | HIV-1 integrase Allosteric inhibitor LEDGF/p75 Dimerization 3-Hydroxypicolinamide |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.10.045 |
| 文献子类 | Article |
| 英文摘要 | Currently, three HIV-1 integrase (IN) active site-directed inhibitors are in clinical use for the treatment of HIV infection. However, emergence of drug resistance mutations have limited the promise of a long-term cure. As an alternative, allosteric inhibition of IN activity has drawn great attention and several of such inhibitors are under early stage clinical development. Specifically, inhibitors of IN and the cellular cofactor LEDGF/p75 remarkably diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity. Distinct from the extensively studied 2-(quinolin-3-yl) acetic acid or 1H-indol-3-yl-2-hydroxy-4-oxobut-2-enoic acid chemotypes, this study discloses a new class of selective IN-LEDGF/p75 inhibitors without the carboxylic acid functionality. More significantly, 3-hydroxypicolinamides also show low micromolar inhibition against IN dimerization, providing novel dual IN inhibitors with in vitro therapeutically selective antiviral effect for further development. Finally, our shape-based ROCS pharmacophore model of the 3-hydroxypicolinamide class of compounds provides a new insight into the binding mode of these novel IN-LEDGF/p75 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | SMALL-MOLECULE INHIBITORS ; SITE INTEGRASE INHIBITOR ; GENETIC ALGORITHM ; BINDING-SITE ; BI 224436 ; REPLICATION ; LEDGF/P75 ; DESIGN ; MULTIMERIZATION ; RECOGNITION |
| 资助项目 | National Natural Science Foundation of China[81325020] ; National Natural Science Foundation of China[81361120410] ; National Natural Science Foundation of China[81321092] ; National Natural Science Foundation of China[81123004] ; National Institutes of Health (NIH/NIAID)[R21 AI081610] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000390496600084 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275684]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Neamati, Nouri; Long, Ya-Qiu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Kunming Inst Zool, Lab Mol Immunopharmacol, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Peoples R China 3.Univ Michigan, Dept Med Chem, Coll Pharm, Ann Arbor, MI 48109 USA; |
| 推荐引用方式 GB/T 7714 | Zhang, Feng-Hua,Debnath, Bikash,Xu, Zhong-Liang,et al. Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,125:1051-1063. |
| APA | Zhang, Feng-Hua.,Debnath, Bikash.,Xu, Zhong-Liang.,Yang, Liu-Meng.,Song, Li-Rui.,...&Long, Ya-Qiu.(2017).Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,125,1051-1063. |
| MLA | Zhang, Feng-Hua,et al."Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 125(2017):1051-1063. |
入库方式： OAI收割
来源：上海药物研究所
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