Prenylated flavanones isolated from flowers of Azadirachta indica (the neem tree) as antimutagenic constituents against heterocyclic amines.
Four prenylated flavanones were isolated from the methanol extract of the flowers of Azadirachta indica (the neem tree) as potent antimutagens against Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) in the Salmonella typhimurium TA98 assay by activity-guided fractionation. Spectroscopic properties revealed that those compounds were 5,7,4'-trihydroxy-8-prenylflavanone (1), 5,4'-dihydroxy-7-methoxy-8-prenylflavanone (2), 5,7,4'-trihydroxy-3',8-diprenylflavanone (3), and 5,7,4'-trihydroxy-3',5'-diprenylflavanone (4). All isolated compounds were found for the first time in this plant. The antimutagenic IC(50) values of compounds 1-4 were 2.7 +/- 0.1, 3.7 +/- 0.1, 11.1 +/- 0.1, and 18.6 +/- 0.1 microM in the preincubation mixture, respectively. These compounds also similarly inhibited the mutagenicity of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). All of the compounds 1-4 strongly inhibited ethoxyresorufin O-dealkylation activity of cytochrome P450 1A isoforms, which catalyze N-hydroxylation of heterocyclic amines. However, compounds 1-4 did not show significant inhibition against the direct-acting mutagen NaN(3). Thus, the antimutagenic effect of compounds 1-4 would be mainly based on the inhibition of the enzymatic activation of heterocyclic amines.
Nakahara
Kazuhiko
K
Japan International Research Center for Agricultural Sciences (JIRCAS), 1-1 Owashi, Tsukuba, Ibaraki 305-8686, Japan. knakahar@jircas.affrc.go.jp
Roy
Molay Kumar
MK
Ono
Hiroshi
H
Maeda
Ikuko
I
Ohnishi-Kameyama
Mayumi
M
Yoshida
Mitsuru
M
Trakoontivakorn
Gassinee
G
D000818:Animals; D016587:Antimutagenic Agents / Q000302:isolation & purification*; D031601:Azadirachta / Q000737:chemistry*; D002243:Carbolines / Q000037:antagonists & inhibitors; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000302:isolation & purification*; D035264:Flowers / Q000737:chemistry*; D005668:Furylfuramide / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D000432:Methanol; D009153:Mutagens / Q000494:pharmacology; D009584:Nitrogen / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology; D017368:Protein Prenylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016587:Antimutagenic Agents; D002243:Carbolines; D004791:Enzyme Inhibitors; D044950:Flavanones; D006571:Heterocyclic Compounds; D009153:Mutagens; D010936:Plant Extracts; D005668:Furylfuramide; C003320:sodium nitride; D019363:Cytochrome P-450 CYP1A1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; D009584:Nitrogen; D000432:Methanol