Studies on panax acetylenes: absolute structure of a new panax acetylene, and inhibitory effects of related acetylenes on the growth of L-1210 cells.
A new Panax acetylene, 3-oxo-PQ-1 (1), was isolated from Panax quinquefolium. The absolute configurations of 3-oxo-PQ-1 (1) and PQ-1 (2) were determined to be (9R,10R) and (3R,9R,10R), respectively, by synthesizing 1 and 2 starting from D-(-)-diethyl tartrate, and by synthesizing their stereoisomers from L-(+)-diethyl tartrate. The growth inhibitory effects of Panax acetylenes (1-8) and their stereoisomers against leukemia cells were tested. Unnatural acetylenes having the (3S)-configuration (2, 5, 6, 7, 8; IC(50)=0.01-0.1 microg/ml) were found to be approximately ten times more potent than natural acetylenes (IC(50)=0.1-1.0 microg/ml) with the (3R)-configuration. Potency differences due to the configuration at C-9 and C-10 were unrelated to this stereochemistry. The C(14)-polyacetylenes, PQ-8 (4) and its isomer (IC(50)=1.0-10.0 microg/ml), were found to exhibit weaker cytotoxicity than the C(17)-polyacetylenes.
Satoh
Yoshio
Y
Showa Pharmaceutical University, Tokyo, Japan.
Satoh
Mitsuru
M
Isobe
Kimiaki
K
Mohri
Kunihiko
K
Yoshida
Yuki
Y
Fujimoto
Yasuo
Y
D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D007939:Leukemia L1210; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D005894:Panax / Q000737:chemistry*; D012015:Reference Standards; D013237:Stereoisomerism
D000480:Alkynes