Structural analysis of a novel antimutagenic compound, 4-hydroxypanduratin A, and the antimutagenic activity of flavonoids in a Thai spice, fingerroot (Boesenbergia pandurata Schult) against mutagenic heterocyclic amines

Six compounds were isolated from fresh rhizomes of fingerroot (Boesenbergia pandurata Schult.) as Strong antimutagens toward 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in Salmonella typhimurium TA98. These compounds were 2 ' ,4 ' ,6 ' -trihydroxychalcone (pinocembrin chalcone; 1), 2 ' ,4 ' -dihydroxy-6 ' -methoxychalcone (cardamonin; 2), 5,7-dihydroxyflavanone (pinocembrin; 3), 5-hydroxy-7-methoxyflavanone (pinostrobin; 4), (2,4,6-trihydroxyphenyl)-[3 ' -methyl-2 '-(3 -methylbut-2 -enyl)-6 ' -phenylcyclohex-3 ' -enyl]methanone (5), and (2,6-dihydroxy-4-methoxyphenyl)- [3 ' -methyl-2 '-(3 -methylbut-2 -enyl)-6 ' -phenylcyclohex-3 ' -enyl]methanone (panduratin A; 6). Compound 5 was a novel compound (tentatively termed 4-hydroxypanduratin A), and 1 was not previously reported in:this plant, whereas 2-4 and 6 were known compounds. The antimutagenic IC50 values of compounds 1-6 were 5.2 +/- 0.4, 5.9 +/- 0.7, 6.9 +/- 0.8, 5.3 +/- 1.0, 12.7 +/- 0.7, and 12.1 +/- 0.8 muM in the preincubation mixture, respectively. They also similarly inhibited the mutagenicity of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All;of them strongly inhibited the N-hydroxylation of Trp-P-2. Thus, the antimutagenic effect of compounds 1-6 was mainly due to the inhibition of the first step of enzymatic activation of heterocyclic amines.