Design, synthesis & structure–activity relationships of a new class of antihuman enterovirus D68 & A71 agents-Reference-Cited by-同舟云学术

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

Published:2018-06-01 Issue:11 Volume:10 Page:1333-1347
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Sethy Bidyadhar¹,Hsieh Chung-Fan²³,Yeh Chieh¹²,Horng Jim-Tong²³⁴⁵,Hsieh Pei-Wen¹⁵⁶⁷

Affiliation:

1. Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan

2. Department of Biochemistry, Chang Gung University, Taoyuan, 33302, Taiwan

3. Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, 33302, Taiwan

4. Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Linkou, 333, Taiwan

5. Research Center for Industry of Human Ecology & Research Center for Chinese Herbal Medicine, Chang Gung University of Science & Technology, Taoyuan, 33303, Taiwan

6. Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, 333, Taiwan

7. Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan

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 (EC50) 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.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

http://www.future-science.com/doi/pdf/10.4155/fmc-2017-0268

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