Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.
Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-β-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 μM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 μM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 μM).
College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Tokyo 101 - 8308, Japan. akihisa.toshihiro@nihon-u.ac.jp
Toshihiro
T
Akihisa
Ayano
A
Takeda
Hiroyuki
H
Akazawa
Takashi
T
Kikuchi
Satoru
S
Yokokawa
Motohiko
M
Ukiya
Makoto
M
Fukatsu
Kensuke
K
Watanabe
D031002:Acer / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D036381:Diarylheptanoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; D008543:Melanins; D010936:Plant Extracts