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

21 Citations (Scopus)

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 - 2014
Externally publishedYes

Fingerprint

Viral Structures
Dengue Virus
Structure-Activity Relationship
Viruses
Derivatives
Dengue
Alkaloids
Aedes
Virus Diseases
Cytotoxicity
Culicidae
Ketones
Antiviral Agents
Vaccines
Flavivirus
Quantitative Structure-Activity Relationship
Bites and Stings
Bioactivity
Cell culture
lycorine

Keywords

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

ASJC Scopus subject areas

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

Cite this

Anti-dengue-virus activity and structure-activity relationship studies of lycorine derivatives. / Wang, Peng; Li, Lin Feng; Wang, Qing Yin; Shang, Lu Qing; Shi, Pei-Yong; Yin, Zheng.

In: ChemMedChem, Vol. 9, No. 7, 2014, p. 1522-1533.

Research output: Contribution to journalArticle

Wang, Peng ; Li, Lin Feng ; Wang, Qing Yin ; Shang, Lu Qing ; Shi, Pei-Yong ; Yin, Zheng. / Anti-dengue-virus activity and structure-activity relationship studies of lycorine derivatives. In: ChemMedChem. 2014 ; Vol. 9, No. 7. pp. 1522-1533.
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