Premium
Cytotoxic and Nitric Oxide Production‐Inhibitory Activities of Limonoids and Other Compounds from the Leaves and Bark of Melia azedarach
Author(s) -
Pan Xin,
Matsumoto Masahiro,
Nishimoto Yuki,
Ogihara Eri,
Zhang Jie,
Ukiya Motohiko,
Tokuda Harukuni,
Koike Kazuo,
Akihisa Momoko,
Akihisa Toshihiro
Publication year - 2014
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201400190
Subject(s) - melia azedarach , chemistry , meliaceae , hl60 , nitric oxide , bark (sound) , nitric oxide synthase , stereochemistry , ic50 , alkaloid , biochemistry , in vitro , botany , biology , organic chemistry , ecology
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 IC 50 values in the range of 2.8–5.8 μ M . 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 IC 50 values in the range of 4.6–87.3 μ M with no, or almost no, toxicity to the cells ( IC 50 93.2–100 μ M ). 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 ( IC 50 299–381 molar ratio/32 pmol TPA) against EpsteinBarr virus early antigen (EBV‐EA) activation induced by 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cell line.