Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents

Bidyadhar Sethy; Chung Fan Hsieh; Chieh Yeh; Jim Tong Horng; Pei Wen Hsieh

doi:10.4155/fmc-2017-0268

Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents

Bidyadhar Sethy, Chung Fan Hsieh, Chieh Yeh, Jim Tong Horng, Pei Wen Hsieh^*

^*Corresponding author for this work

Chang Gung University

Research output: Contribution to journal › Journal Article › peer-review

2 Scopus citations

Abstract

Aim: No antiviral medications are currently approved to treat enterovirus (EV)-associated disease or prevent EV infection. Methods: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents. Results: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC ₅₀ ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively. Conclusion: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.

Original language	English
Pages (from-to)	1333-1347
Number of pages	15
Journal	Future Medicinal Chemistry
Volume	10
Issue number	11
DOIs	https://doi.org/10.4155/fmc-2017-0268
State	Published - 06 2018

Bibliographical note

Publisher Copyright:
© 2018 Newlands Press.

Keywords

EV A71
EV D68
metabolic stability
optimization
probenecid derivatives

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title = "Design, synthesis \& structure-activity relationships of a new class of antihuman enterovirus D68 \& A71 agents",

abstract = " Aim: No antiviral medications are currently approved to treat enterovirus (EV)-associated disease or prevent EV infection. Methods: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents. Results: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC 50 ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively. Conclusion: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.",

keywords = "EV A71, EV D68, metabolic stability, optimization, probenecid derivatives",

author = "Bidyadhar Sethy and Hsieh, \{Chung Fan\} and Chieh Yeh and Horng, \{Jim Tong\} and Hsieh, \{Pei Wen\}",

note = "Publisher Copyright: {\textcopyright} 2018 Newlands Press.",

year = "2018",

month = jun,

doi = "10.4155/fmc-2017-0268",

language = "英语",

volume = "10",

pages = "1333--1347",

journal = "Future Medicinal Chemistry",

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publisher = "Taylor and Francis Ltd.",

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T1 - Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents

AU - Sethy, Bidyadhar

AU - Hsieh, Chung Fan

AU - Yeh, Chieh

AU - Horng, Jim Tong

AU - Hsieh, Pei Wen

PY - 2018/6

Y1 - 2018/6

N2 - Aim: No antiviral medications are currently approved to treat enterovirus (EV)-associated disease or prevent EV infection. Methods: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents. Results: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC 50 ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively. Conclusion: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.

AB - Aim: No antiviral medications are currently approved to treat enterovirus (EV)-associated disease or prevent EV infection. Methods: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents. Results: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC 50 ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively. Conclusion: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.

KW - EV A71

KW - EV D68

KW - metabolic stability

KW - optimization

KW - probenecid derivatives

UR - https://www.scopus.com/pages/publications/85048232263

U2 - 10.4155/fmc-2017-0268

DO - 10.4155/fmc-2017-0268

M3 - 文章

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SN - 1756-8919

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ER -

Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents

Abstract

Bibliographical note

Keywords

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