Discovery of 3-Amino-2-Hydroxypropoxyisoflavone Derivatives as Potential Anti-HCV Agents
Synthesis and anti-hepatitis C virus (anti-HCV) effects of certain 3-amino-2-hydroxy-propoxy isoflavone derivatives, ⁻ , were described. The known 3-(3,4-dimethoxyphenyl)-7-(oxiran-2-ylmethoxy)-4 -chromen-4-one ( ) was reacted with substituted amines to give the desired isoflavone derivatives, ⁻ . A...
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Published in | Molecules (Basel, Switzerland) Vol. 23; no. 11; p. 2863 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
02.11.2018
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | Synthesis and anti-hepatitis C virus (anti-HCV) effects of certain 3-amino-2-hydroxy-propoxy isoflavone derivatives,
⁻
, were described. The known 3-(3,4-dimethoxyphenyl)-7-(oxiran-2-ylmethoxy)-4
-chromen-4-one (
) was reacted with substituted amines to give the desired isoflavone derivatives,
⁻
. Among them, 7-{3-[(3,4-dimethoxy-phenethyl)amino]-2-hydroxypropoxy}-3-(3,4-dimethoxyphenyl)-4
-chromen-4-one (
) was the most active, exhibiting approximately 2-fold higher anti-HCV effects than standard antiviral drug ribavirin (EC
of 6.53 vs. 13.16 μM). In addition, compound
was less cytotoxic than ribavirin. The selectivity index (SI) of
is approximately 2.6-fold higher than ribavirin. The compounds
,
, and
were also found to possess higher anti-HCV effects than ribavirin. Compound
was found to inhibit the HCV RNA expression in Ava5 cells in a dose-dependent manner; furthermore, we found that the antiviral mechanism of compounds
,
,
, and
gave rise to induction of HO-1 expression. With the HO-1 promoter-based analysis, we found compounds
,
,
, and
induced HO-1 expression through increasing Nrf-2 binding activity. Taken together, compound
may serve as a potential lead compound for developing novel anti-HCV agents. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1420-3049 1420-3049 |
DOI: | 10.3390/molecules23112863 |