title: Cytotoxic activity of butane type of 1,7-seco-2,7'-cyclolignanes and apoptosis induction by Caspase 9 and 3.
abstract: All stereoisomers of methoxybutane and fluorobutane type of 1,7-seco-2,7'-cyclolignane were synthesized and cytotoxic activities of these compounds were compared with those of all stereoisomers of butane and butanol type compounds. Both enantiomers of butane type secocyclolignane showed higher cytotoxic activity (IC50=16-20 μM) than methoxy type compounds, whereas none was observed for all the stereoisomers of butanol type secocyclolignane, however, (-)-Kadangustin J showed stereospecific cytotoxic activity (IC50=47-67 μM). Since (R)-9'-fluoro derivative 23 was most potent (IC50=19 μM) among the corresponding fluoro stereoisomers, (R)-9'-alkyl derivatives were synthesized, hydrophobic 9'-heptyl derivative 27 showing highest activity (IC50=3.7 μM against HL-60, IC50=3.1 μM against HeLa) in this experiment. Apoptosis induction caused by Caspase 3 and 9 for (R)-9'-heptyl derivative 27 was observed in the research on the mechanism. A degradation of DNA into small fragments was also shown by DNA ladder assay.
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Tuti
authors.initials: T
authors.lastname: Wukirsari
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nishiwaki
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugahara
authors.affiliation: Integrated Center for Sciences, Tarumi Station, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan. Electronic address: syamauch@agr.ehime-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamauchi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002073:Butanes / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: C000595932:9'a,9'b,9'c,9'd,9'e,9'f,9'g-heptahomo-1,7-seco-2,7'-cyclolignane-4',5-diol; D002073:Butanes; D017705:Lignans; D053148:Caspase 3; D053453:Caspase 9
keywords: 1,7-Seco-2,7′-cyclolignane; Apoptosis; Caspase; Cytotoxic activity; Kadangustin J; Lignan; Neolignan