Lipase-catalyzed preparation of optically active 1'-acetoxychavicol acetates and their structure-activity relationships in apoptotic activity against human leukemia HL-60 cells.
Structure-activity relationships of 1'-acetoxychavicol acetate (ACA) for apoptotic activity against human leukemia HL-60 cells were investigated using optically active ACA and various racemic ACA analogues. Natural-type (or with different acyl group) ACA showed a high apoptotic activity, but the ortho or meta isomers, 4-deacetoxy analogue, and the 2'-3' dehydrogenated derivative had no effect, or a weak activity. Optically active (R)- and (S)-ACA were prepared by a lipase-catalyzed esterification. Using a mixture of vinyl acetate-tetrahydrofuran (1:1 v/v) as a solvent at refluxing temperature, optically pure (R)- and (S)-ACA were obtained (99.7% ee and 99.1% ee, respectively). The apoptosis-inducing effects of both enantiomers were compared by means of an MTT assay and the detection of typical apoptotic phenomena (DNA fragmentation, caspase-3 activation, and PARP cleavage) and these two activities were almost equal. These results indicate that the essential moieties of ACA for apoptotic activity against HL-60 cells are both the presence of a 4-acetoxyl group and an unsaturated double bond between C-2' and C-3', and that the configuration at the 1'-position is unrelated to activity.
Azuma
Hideki
H
Department of Applied and Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Osaka 558-8585, Japan. azumah@bioa.eng.osaka-cu.ac.jp
Miyasaka
Keita
K
Yokotani
Tsuyoshi
T
Tachibana
Taro
T
Kojima-Yuasa
Akiko
A
Matsui-Yuasa
Isao
I
Ogino
Kenji
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001592:Benzyl Alcohols; D002384:Catalysis; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001592:Benzyl Alcohols; D013729:Terpenes; D008049:Lipase; C047948:1'-acetoxychavicol acetate