Plant Antiviral Agents; VI.1 3-Methoxyflavones as Potent Inhibitors of Viral-Induced Block of Cell Synthesis.

An investigation of the constituents responsible for the pronounced antiviral activity observed for extracts of EUPHORBIA GRANTII Oliv. stems has afforded four related 3-methoxyflavones exhibiting remarkable activities against picornaviruses and vesicular stomatitis virus. All compounds were found to be derivatives of 3-methylquercetin. The concentration of 3-methylquercetin (3-MQ) and 3,3'-dimethyl-quercetin (3,3'-DMQ) inhibiting 90 % of polio type 1 and coxsackie B4 viruses in tissue culture was about 0.01 microg/ml, whereas the 50 % cytotoxic concentration was 40 microg/ml. When administered intraperitoneally, 3-MQ protected mice from viremia and lethal infections from coxsac kie B4 virus at a daily dose of 20 mg/kg for a period of nine days. Biochemical studies on the mechanism of action of 3-MQ or 3,3'-DMQ on poliovirus replication suggested that these 3-methoxyflavones are able to protect the host cells from a viral induced shutdown of the cellular protein synthesis. Preliminary structure activity relationship studies have shown the 3-methoxyfunction of the flavones to be essential for the observed antiviral effects.