medicinal chemistry, natural products,
photochemistry reactivity, aporphine and oxoaporphine,
oxoisoaporphine, coumarins
Manuscript ID: molecules-aporph-20080915-tw-Chen
Type of Paper: Article
Tentative Title: Liriodenine Compound Inhibits
in vitro Dengue Virus Replication
or Anti-dengue Viral Activity of Liriodenine Derivatives
Authors: Chung-Yi Chen
Affiliation: School of Medicine and Health Sciences, Fooyin University, Kaohsiung Hsien 831, Taiwan
E-mail:
[email protected]Abstract: Dengue viruses
(DV)
are mosquito-borne
flaviviruses that
cause a large number of human infections worldwide each year. No vaccines or
chemotherapeutics are currently available.
Therefore, the increasing number of outbreaks of dengue hemorrhagic
fever caused by DV infection brings out an urgent need to develop potent anti-DV
agents. A collection of hundreds of pure components isolated from the native
plants of
Taiwan,
we found purified compounds of
Michelia alba for the activities to
suppress DV replication using a stable subgenomic dengue virus replicon system
that expressed firefly luciferase reporter and neomycin phosphotransferase
(Neo) genes in BHK21 cell lines. The results indicated
that the liriodenine (aporphime) compound can significantly reduce luciferase-reporter
activity in a dose dependent manner. The 50% effective concentration
(EC50) was 22.0 +/- 2.0
mM and no mitrochondrial toxicity was
observed at this effective concentration.
Furthermore, the liriodenine compound
exhibited a synergistic antiviral activity in combination with IFN
-α in DV
replicon system, in which the antiviral response was better than IFN
-αalone. Collectively,
these data suggested that this novel inhibitor could be developed for potential
treatment of DV infection through combination with other therapeutics.