| RRC ID |
42490
|
| Author |
Azuma H, Miyasaka K, Yokotani T, Tachibana T, Kojima-Yuasa A, Matsui-Yuasa I, Ogino K.
|
| Title |
Lipase-catalyzed preparation of optically active 1'-acetoxychavicol acetates and their structure-activity relationships in apoptotic activity against human leukemia HL-60 cells.
|
| Journal |
Bioorg Med Chem
|
| Abstract |
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.
|
| Volume |
14(6)
|
| Pages |
1811-8
|
| Published |
2006-3-15
|
| DOI |
10.1016/j.bmc.2005.10.029
|
| PII |
S0968-0896(05)01017-5
|
| PMID |
16288877
|
| MeSH |
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Apoptosis* / drug effects
Benzyl Alcohols
Catalysis
Cells, Cultured
Drug Screening Assays, Antitumor
HL-60 Cells
Humans
Lipase / metabolism*
Molecular Structure
Stereoisomerism
Structure-Activity Relationship
Terpenes / chemical synthesis
Terpenes / chemistry*
Terpenes / pharmacology
|
| IF |
3.073
|
| Times Cited |
19
|
|
WOS Category
|
CHEMISTRY, ORGANIC
CHEMISTRY, MEDICINAL
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
