Cytotoxic activity of dietary lignan and its derivatives: structure-cytotoxic activity relationship of dihydroguaiaretic acid.
Cytotoxic activities of synthesized lignan derivatives were estimated by WST-8 reduction assay against HL-60 and HeLa cells to show the structure-activity relationship. The activities of some effective compounds were examined against Colon 26 and Vero cells. Dietary secoisolariciresinol (SECO, 1) and its metabolite, 9,9'-anhydrosecoisolariciresinol (2), did not show the cytotoxic activity. On the other hand, all stereoisomers of dihydroguaiaretic acid (DGA, 9,9'-dehydroxysecoisolariciresinol, 3-5) exhibited the activity (IC50: around 30 μM). The IC50 value of (8R,8'R)-9-butyl DGA derivative 13 was around 6 μM. This fact means that the hydrophobic group was advantageous for higher activity at 9- and 9'-positions. By the evaluation of the effect of 7and 7'-aryl group on the activity, we discovered the highest activity of (8R,8'R)-7-(3-hydroxy-4-methoxyphenyl)-7'-(2-ethoxyphenyl) DGA derivative 47 showing around 1 μM of IC50 value, which is about 24-fold higher activity than that of natural (8R,8'R)-DGA. The derivative of dietary lignan showed the high cytotoxic activity.
Faculty of Agriculture and §Integrated Center for Sciences, Tarumi Station, Ehime University , 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
Tuti
T
Wukirsari
Hisashi
H
Nishiwaki
Kosuke
K
Nishi
Takuya
T
Sugahara
Koichi
K
Akiyama
Taro
T
Kishida
Satoshi
S
Yamauchi
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D018922:HL-60 Cells; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014709:Vero Cells
D003603:Cytotoxins; D017705:Lignans; C015816:dihydroguaiaretic acid; D006139:Guaiacol