Anti-dengue-virus activity and structure-activity relationship studies of lycorine derivatives

Peng Wang, Lin Feng Li, Qing Yin Wang, Lu Qing Shang, Pei Yong Shi, Zheng Yin

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Dengue is a systemic viral infection that is transmitted to humans by Aedes mosquitoes. No vaccines or specific therapeutics are currently available for dengue. Lycorine, which is a natural plant alkaloid, has been shown to possess antiviral activities against flaviviruses. In this study, a series of novel lycorine derivatives were synthesized and assayed for their inhibition of dengue virus (DENV) in cell cultures. Among the lycorine analogues, 1-acetyllycorine exhibited the most potent anti-DENV activity (EC50=0.4 μM) with a reduced cytotoxicity (CC50>300 μM), which resulted in a selectivity index (CC50/EC50) of more than 750. The ketones 1-acetyl-2-oxolycorine (EC50=1.8 μM) and 2-oxolycorine (EC50=0.5 μM) also exhibited excellent antiviral activities with low cytotoxicity. Structure-activity relationships for the lycorine derivatives against DENV are discussed. A three-dimensional quantitative structure-activity relationship model was established by using a comparative molecular-field analysis protocol in order to rationalize the experimental results. Further modifications of the hydroxy group at the C1 position with retention of a ketone at the C2 position could potentially lead to inhibitors with improved overall properties. Alkaloids that bite back: Dengue is a systemic viral infection that is transmitted to humans by Aedes mosquitoes. Currently, vaccines or specific therapeutics are not available. Lycorine, which is a natural alkaloid, has reportedly demonstrated biological activity against dengue virus (DENV). A series of lycorine derivatives and their anti-DENV activities are reported herein.

Original languageEnglish (US)
Pages (from-to)1522-1533
Number of pages12
JournalChemMedChem
Volume9
Issue number7
DOIs
StatePublished - Jul 2014
Externally publishedYes

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Keywords

  • alkaloids
  • antiviral agents
  • dengue virus
  • lycorine
  • structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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