Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 187, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111925
Keywords
Zika virus; Antiviral; Andrographolide and derivative; Quinolyloxy; 14 alpha-(8 '-quinolyloxy)
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Funding
- National Natural Science Foundation of China [30973621, U0632001]
- National Institutes of Health, USA [U19 AI131130]
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The Zika endemic established by imported and local transmission is of significant concern and effective anti-ZIKV drugs remain an urgent unmet need. As andrographolide was identified to be an inhibitor of DENV and CHIKV and the importance of quinoline structure against infectious diseases was considered, we are interested in studying its andrographolide derivatives with quinoline moiety against Zika virus infection. In addition to screening eight in-house derivatives of andrographolide, sixteen new derivatives were designed, synthesized and tested against Zika virus infection. Among these compounds, two most potent anti-Zika compounds of 19-acetylated 14 alpha,-(5',7'-dichloro-8'-quinolyloxy) derivative 17b and 14 beta-(8'-quinolyloxy)-3,19- diol derivative 3 with the highest selectivity were discovered. The SAR analysis indicates that rational and optimal combined modification/s at 3-, 14-, or 19-positions can make derivatives less toxic and more potent against Zika infection, and both of 3 and 17b are suitable as leads for designing new generation of andrographolide derivatives with quinoline or its structure- and property related moieties against Zika virus and other arboviruses. (C) 2019 Elsevier Masson SAS. All rights reserved.
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