Moscatilin from Dendrobium nobile, a naturally occurring bibenzyl compound with potential antimutagenic activity.
A bibenzyl compound that possesses antimutagenic activity was isolated from the storage stem of Dendrobium nobile. The isolated compound suppressed the expression of the umu gene following the induction of SOS response in Salmonella typhimurium TA1535/pSK1002 that have been treated with various mutagens. The suppressive compound was mainly localized in the n-hexane extract fraction of the processed D. nobile. This n-hexane fraction was further fractionated by silica gel column chromatography, which resulted in the purification and subsequent identification of the suppressive compound. EI-MS and (1)H and (13)C NMR spectroscopy were then used to delineate the structure of the compound that confers the observed antimutagenic activity. Comparison of the obtained spectrum with that found in the literature indicated that moscatilin is the secondary suppressive compound. When using 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) as the mutagen, moscatilin suppressed 85% of the umu gene expression compared to the controls at <0.73 micromol/mL, with an ID(50) value of 0.41 micromol/mL. Additionally, moscatilin was tested for its ability to suppress the mutagenic activity of other well-known mutagens such as 4-nitroquinoline-1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), UV irradiation, 3-amino-1,4-dimethyl-5H-pyrido[4,3b]indole (Trp-P-1), benzo[a]pyrene (B[a]P), and aflatoxin B(1) (AFB(1)). With all of the aforementioned chemicals or treatments, moscatilin showed a dramatic reduction in their mutagenic potential. Interestingly, moscatilin almost completely suppressed (97%) the AFB(1)-induced SOS response at concentrations <0.73 micromol/mL, with an ID(50) of 0.08 micromol/mL. Finally, the antimutagenic activities of moscatilin against furylfuramide and Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain. The results those experiments indicated that moscatilin demonstrated a dramatic suppression of the mutagenicity of only Trp-P-1 but not furylfuramide.
Miyazawa
M
M
Department of Applied Chemistry, Kinki University, Kowakae, Osaka, Japan. miya-zawa@apch.kindai.ac.jp
Shimamura
H
H
Nakamura
S
S
Sugiura
W
W
Kosaka
H
H
Kameoka
H
H
D016587:Antimutagenic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001593:Benzyl Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006586:Hexanes; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000737:chemistry; D018547:Plant Stems; D010946:Plants, Medicinal / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000187:drug effects
D016587:Antimutagenic Agents; D001593:Benzyl Compounds; D006586:Hexanes; D010936:Plant Extracts; C071845:dendrophenol; C026385:n-hexane