Anti-tyrosinase and anti-cancer activities of flavonoids from Blumea balsamifera DC

Fractionation of an ethylacetate extract from leaves of Blumea balsamifera DC, led to isolation of nine flavonoids. The isolated compounds consisted of two dihydroflavonols, dihydroquercetin-4¢-methyl ether (1) and dihydroquercetin-7,4¢-dimethyl ether (2), two flavanones, 5,7,3¢,5¢-tetrahydroxyflavanone (3) and blumeatin (4), three flavonols, quercetin(5), rhamnetin (6) and tamarixetin (7), two flavones, luteolin (8) and luteolin-7-methyl ether (9). Their chemical structures were elucidated by spectroscopic methods including UV, NMR and MS analyses. Their inhibitory activities on mushroom tyrosinase using L-DOPA as substrate were evaluated. The anti-tyrosinase activities of dihydroflavonols (1 and 2) and flavonols (5-7) are stronger than arbutin, whereas flavanones (3 and 4) and flavones (8 and 9) are weaker than arbutin. The kinetic analysis showed that the dihydroflavonols (1 and 2), flavanones (3), and flavonols (5 and 6) are competitive inhibitors, whereas the flavones (8 and 9) are noncompetitive inhibitors. The inhibition constant (KI) of compounds 1-3 were determined to be 0.10, 0.08, and 0.33 mM, respectively. Some compounds (1-5 and 9) were evaluated for cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines.Compounds 2, 4, and 9 were active against the KB cells with the IC50 values of 17.09, 47.72 and 17.83 ug/ml, respectively. Compounds 2, 3 and 5 exhibited moderate activity against the NCI-H187 cells with the IC50 values of 16.29, 29.97 and 20.59 ug/ml. Luteolin-7-methyl ether (9) showed strong cytotoxicity against human lung cancer (NCI-H187) cell lines with IC50 of 1.29 µg/ml and moderate toxicity against oral cavity cancer (KB) cell lines with IC50 of 17.83 µg/ml.   Key words: Blumea Balsamifera DC, cytotoxicity, flavanoids, tyrosinase inhibitor.