title: Prenylated flavanones isolated from flowers of Azadirachta indica (the neem tree) as antimutagenic constituents against heterocyclic amines.
abstract: 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.
authors.affiliation: Japan International Research Center for Agricultural Sciences (JIRCAS), 1-1 Owashi, Tsukuba, Ibaraki 305-8686, Japan. knakahar@jircas.affrc.go.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Molay Kumar
authors.initials: MK
authors.lastname: Roy
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.forename: Ikuko
authors.initials: I
authors.lastname: Maeda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ohnishi-Kameyama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Gassinee
authors.initials: G
authors.lastname: Trakoontivakorn
mesh_terms: 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
chemical_list: 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