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. siamensisValeton (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 -melanocyte-stimulating hormone (-MSH). Compound 2 (16.9% melanin content at 30M), 6-deacetylnimbin (3; 49.6% melanin content at 100M), and kaempferide (10; 41.7% melanin content at 10M) 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 4.5-9.9M.