Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors

Guo Chun Zhou; Zhibing Weng; Xiaoxia Shao; Fang Liu; Xin Nie; Jinsong Liu; Decai Wang; Chunguang Wang; Kai Guo

doi:10.1016/j.bmcl.2013.10.071

Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors

Guo Chun Zhou, Zhibing Weng, Xiaoxia Shao, Fang Liu, Xin Nie, Jinsong Liu, Decai Wang, Chunguang Wang, Kai Guo

生物与制药工程学院

科研成果: 期刊稿件 › 文章 › 同行评审

31 引用（Scopus）

摘要

A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with K_i values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that l-proline, l-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.

源语言	英语
页（从-至）	6549-6554
页数	6
期刊	Bioorganic and Medicinal Chemistry Letters
卷	23
期	24
DOI	https://doi.org/10.1016/j.bmcl.2013.10.071
出版状态	已出版 - 15 12月 2013

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10.1016/j.bmcl.2013.10.071

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title = "Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors",

abstract = "A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that l-proline, l-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.",

keywords = "4-Nitroaniline, Dengue virus NS2B-NS3 protease, Methionine, Methionine-proline anilides, Proline",

author = "Zhou, {Guo Chun} and Zhibing Weng and Xiaoxia Shao and Fang Liu and Xin Nie and Jinsong Liu and Decai Wang and Chunguang Wang and Kai Guo",

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T1 - Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors

AU - Zhou, Guo Chun

AU - Weng, Zhibing

AU - Shao, Xiaoxia

AU - Liu, Fang

AU - Nie, Xin

AU - Liu, Jinsong

AU - Wang, Decai

AU - Wang, Chunguang

AU - Guo, Kai

PY - 2013/12/15

Y1 - 2013/12/15

N2 - A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that l-proline, l-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.

AB - A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that l-proline, l-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.

KW - 4-Nitroaniline

KW - Dengue virus NS2B-NS3 protease

KW - Methionine

KW - Methionine-proline anilides

KW - Proline

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AN - SCOPUS:84888868309

SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors

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