RRC ID 67896
Author Pan X, Matsumoto M, Nishimoto Y, Ogihara E, Zhang J, Ukiya M, Tokuda H, Koike K, Akihisa M, Akihisa T.
Title Cytotoxic and nitric oxide production-inhibitory activities of limonoids and other compounds from the leaves and bark of Melia azedarach.
Journal Chem Biodivers
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.
Volume 11(8)
Pages 1121-39
Published 2014-8-1
DOI 10.1002/cbdv.201400190
PMID 25146759
MeSH Animals Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / pharmacology* Cell Line, Tumor Cyclooxygenase 2 Inhibitors / pharmacology Cyclooxygenase Inhibitors / pharmacology HL-60 Cells Humans Inhibitory Concentration 50 Limonins / chemistry Limonins / isolation & purification Limonins / pharmacology* Macrophages / drug effects Macrophages / metabolism Melia azedarach / chemistry* Mice Molecular Structure Nitric Oxide / metabolism* Nitric Oxide Synthase Type II / antagonists & inhibitors Nitric Oxide Synthase Type II / metabolism Plant Bark / chemistry Plant Leaves / chemistry
IF 2.039
Human and Animal Cells HL60 A549