7-O-Arylmethylgalangin as a novel scaffold for anti-HCV agents.
In spite of potent antiviral activity, suboptimal physicochemical properties of aryl diketo acids (ADKs) necessitates modification of the core 1,3-diketo acid functionality into a novel scaffold. As the metal-binding affinity of the diketo acid is the key to the antiviral activity of ADKs, we anticipated 3,5-dihydroxy-4-oxo arrangement of galangin scaffold would serve as an excellent mimic for the diketo acid functionality. In this study, through synthesis and biological evaluation of various galangin derivatives, we have shown that the diketo acid functionality can be successfully replaced with the galangin scaffold by specific combination of the substituents to result in identification of a novel galangin derivative (3s) with anti-HCV activity (EC(50)=0.9 μM) comparable to the ADK counterpart.
Lee
Hyo Seon
HS
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Park
Kwang-su
KS
Lee
Chaewoon
C
Lee
Bokhui
B
Kim
Dong-Eun
DE
Chong
Youhoon
Y
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects; D007651:Keto Acids / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D005419:Flavonoids; D007651:Keto Acids; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C037032:galangin; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase