title: Cytotoxic and nitric oxide production-inhibitory activities of limonoids and other compounds from the leaves and bark of Melia azedarach.
abstract: Nine limonoids, 1-9, one apocarotenoid, 11, one alkaloid, 12, and one steroid, 13, from the leaf extract; and one triterpenoid, 10, five steroids, 14-18, and two flavonoids, 19 and 20, from the bark extract of Melia azedarach L. (Chinaberry tree; Meliaceae) were isolated. Among these compounds, three compounds, 4-6, were new, and their structures were established as 3-deacetyl-28-oxosalannolactone, 3-deacetyl-28-oxosalanninolide, and 3-deacetyl-17-defurano-17,28-dioxosalannin, respectively, on the basis of extensive spectroscopic analyses and comparison with literature data. All of the isolated compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines. 3-Deacetyl-4'-demethyl-28-oxosalannin (3) against HL60 and AZ521 cells, and methyl kulonate (10) against HL60 cells exhibited potent cytotoxicities with IC50 values in the range of 2.8-5.8 μM. In addition, upon evaluation of compounds 1-13 against production of nitric oxide (NO) in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), seven, i.e., trichilinin B (1), 4, ohchinin (7), 23-hydroxyohchininolide (8), 21-hydroxyisoohchininolide (9), 10, and methyl indole 3-carboxylate (12), inhibited production of NO with IC50 values in the range of 4.6-87.3 μM with no, or almost no, toxicity to the cells (IC50 93.2-100 μM). Western blot analysis revealed that compound 7 reduced the expression levels of the inducible NO synthase (iNOS) and COX-2 proteins in a concentration-dependent manner. Furthermore, compounds 5, 6, 13, and 18-20 exhibited potent inhibitory effects (IC50 299-381 molar ratio/32 pmol TPA) against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cell line.
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Pan
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Ogihara
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Motohiko
authors.initials: M
authors.lastname: Ukiya
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
authors.forename: Momoko
authors.initials: M
authors.lastname: Akihisa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D031586:Melia azedarach / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry
chemical_list: C000597847:3-deacetyl-17-defurano-17,28-dioxosalannin; C000597846:3-deacetyl-28-oxosalanninolide; C000597845:3-deacetyl-28-oxosalannolactone; D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D036701:Limonins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Cytotoxic activity; EpsteinBarr virus early antigen; Limonoids; Melia azedarach; NO Production-inhibitory activity; Triterpenoids