Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities.
A new limonoid, 7-O-acetyl-7-O-debenzoyl-22-hydroxy-21-methoxylimocinin (2), and two new flavonoids, 3'-(3-hydroxy-3-methylbutyl)naringenin (7) and 4'-O-methyllespedezaflavanone C (9), along with nine known compounds, including two limonoids, 1 and 3, and seven flavonoids, 4-6, 8, and 10-12, were isolated from a MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their melanogenesis-inhibitory activities in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH). Compound 2 (16.9% melanin content at 30 μM), 6-deacetylnimbin (3; 49.6% melanin content at 100 μM), and kaempferide (10; 41.7% melanin content at 10 μM) exhibited inhibitory effects with no, or almost no, toxicity to the cells (81.0-111.7% cell viability). In addition, evaluation of their cytotoxic activities against HL60, A549, AZ521, and SK-BR-3 human cancer cell lines, isoazadironolide (1), 4'-O-methyl-8-prenylnaringenin (5), euchrestaflavanone A (8), 9, and 3-methoxy-3'-prenylnaringenin (12) revealed potent cytotoxicities against one or more cell lines with IC50 values in the range of 4.5-9.9 μM.
Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand (phone: +66-53-944338; fax: +66-53-894169).
Worapong
W
Kitdamrongtham
Kenta
K
Ishii
Kodai
K
Ebina
Jie
J
Zhang
Motohiko
M
Ukiya
Kazuo
K
Koike
Hiroyuki
H
Akazawa
Aranya
A
Manosroi
Jiradej
J
Manosroi
Toshihiro
T
Akihisa
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031601:Azadirachta / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D036701:Limonins; D008543:Melanins
Azadirachta indica var. siamensis; Cytotoxic activity; Flavonoids; Limonoids; Melanogenesis-inhibitory activity; Siamese neem tree