Robustaflavone, a potential non-nucleoside anti-hepatitis B agent

• Published in: Antiviral research 1998-08, Vol.39 (2), p.81-88
• Main Authors: Zembower, David E, Lin, Yuh-Meei, Flavin, Michael T, Fa-Ching Chen, Korba, Brent E
• Format: Article
• Language: English
• Subjects: Acyclovir - analogs & derivatives; Acyclovir - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Biflavanoid; Biflavonoids; Biological and medical sciences; Cell Line; Combination therapy; Drug Synergism; Flavonoids - pharmacology; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - physiology; Lamivudine - pharmacology; Medical sciences; Microbial Sensitivity Tests; Natural product; Non-nucleoside antiviral agent; Pharmacology. Drug treatments; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(98)00033-3

Robustaflavone, a naturally occurring biflavanoid isolated from Rhus succedanea, was found to be a potent inhibitor of hepatitis B virus (HBV) replication in 2.2.15 cells, with an effective concentration (EC 50) of 0.25 μM, and a selectivity index (SI, IC 50/EC 90) of 153. Robustaflavone hexaacetate inhibited HBV replication with an EC 50 of 0.73 μM, but exhibited no cytotoxicity at concentrations up to 1000 μM. Combinations of robustaflavone with penciclovir and lamivudine displayed synergistic anti-HBV activity, having the most pronounced effects when the combination ratios were similar to the ratio of EC 50 potencies. Thus, a 1:1 combination of robustaflavone and penciclovir exhibited an EC 50 of 0.11 μM and an SI of 684, while a 10:1 combination of robustaflavone and lamivudine exhibited an EC 50 of 0.054 μM and an SI of 894. Statistical analyses of the combination data using the Combostat® program confirmed that robustaflavone exhibited synergism with both penciclovir and lamivudine.