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 inMolecules (Basel, Switzerland) Vol. 23; no. 11; p. 2863
Main Authors Lee, Jin-Ching, Lin, Chun-Kuang, Tseng, Chin-Kai, Chen, Yeh-Long, Tzeng, Cherng-Chyi, Tseng, Chih-Hua
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 02.11.2018
MDPI
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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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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules23112863