4'-Hydroxy-3-methoxyflavones with potent antipicornavirus activity

Article abstract of DOI:10.1021/jm00106a039

4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI₉₉ values of > 1000 and > 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC₅₀ values ranging from 0.016 to 0.5 μg/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.