2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies
文献类型：期刊论文
| 作者 | Zhu, Jin2; Chen, Tong2; Chen, Lili1 ; Lu, Weiqiang2; Che, Peng2; Huang, Jin2; Li, Honglin2; Li, Jian2; Jiang, Hualiang1,2
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| 刊名 | MOLECULES
 |
| 出版日期 | 2009-01 |
| 卷号 | 14期号:1页码:494-508 |
| 关键词 | 3-(1H-Indol-3-yl)-propanamide derivatives Falcipain-2 inhibitor Malaria SAR |
| ISSN号 | 1420-3049 |
| DOI | 10.3390/molecules14010494 |
| 文献子类 | Article |
| 英文摘要 | The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide (1), which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR)-based binding assays. Four compounds - 1, 2b, 2k and 21 - showed moderate FP-2 inhibition activity, with IC50 values of 10.0-39.4 mu M, and the inhibitory activity of compound 2k was similar to 3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity. |
| WOS关键词 | CYSTEINE PROTEASE INHIBITORS ; PLASMODIUM-FALCIPARUM ; RECOMBINANT FALCIPAIN-2 ; CHLOROQUINE RESISTANCE ; DRUG RESISTANCE ; PROTEINASE ; IDENTIFICATION ; DERIVATIVES ; HEMOGLOBINASE ; DISCOVERY |
| 资助项目 | National Natural Science Foundation of China[90813005] ; National Natural Science Foundation of China[30672539] ; National Natural Science Foundation of China[20803022] ; 863 Hi-Tech Program of China[2006AA020404] ; 863 Hi-Tech Program of China[2007AA02Z147] ; 863 Hi-Tech Program of China[2007AA02Z304] ; Shanghai Committee of Science and Technology[08JC1407800] ; Shanghai Ministry of Science and Technology[07QA14013] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000262791200039 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279398]  |
| 专题 | 生物技术药物研发中心（筹） 药物发现与设计中心 |
| 通讯作者 | Huang, Jin |
| 作者单位 | 1.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhu, Jin,Chen, Tong,Chen, Lili,et al. 2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies[J]. MOLECULES,2009,14(1):494-508. |
| APA | Zhu, Jin.,Chen, Tong.,Chen, Lili.,Lu, Weiqiang.,Che, Peng.,...&Jiang, Hualiang.(2009).2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies.MOLECULES,14(1),494-508. |
| MLA | Zhu, Jin,et al."2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies".MOLECULES 14.1(2009):494-508. |
入库方式： OAI收割
来源：上海药物研究所
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