Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria

Abstract

A new chromone, 2-(2-hydroxy-2-phenylethyl)chromone (<b>1</b>), was isolated together with ten known phenylethyl chromones from MeOH extracts of agarwood (<i>Aquilaria filaria</i>). The selected compounds were evaluated in an antiproliferative assay against five human tumor cell lines, including a multidrug-resistant cell line. They were also tested for antitumor promoting activity, as mediated by 12-<i>O</i>-tetradecanoylphorbol-13-acetate-induced activation of the Epstein-Barr virus early antigen in Raji cells. Among all compounds, 4',7-dimethyoxy-6-hydroxychromone (<b>2</b>) displayed broad spectrum antiproliferative activity against all tumor cell lines tested with IC₅₀ values of 25-38 µM, while <b>8</b> was selectively inhibitory against multidrug-resistant cells. All tested compounds suppressed tumor promotion at noncytotoxic concentrations. 4',6-Dihydroxyphenylethylchromone (<b>7</b>) exhibited the most potent effect with an IC₅₀ value of 319 mol ratio relative to 12-<i>O</i>-tetradecanoylphorbol-13-acetate. This study is the first to report the antitumor promoting activity of 2-(2-phenylethyl)chromone derivatives, as well as the selective antiproliferative activity of <b>8</b> against a multidrug-resistant tumor cell line.