Arteminolides B, C, and D, new inhibitors of farnesyl protein transferase from Artemisia argyi.
Arteminolides B-D (2-4), new farnesyl protein transferase inhibitors, were isolated together with a known arteminolide A (1) and new regioisomers (5-7) of the compounds from the aerial parts of Artemisia argyi. Structures of these compounds were elucidated by spectroscopic methods and chemical conversion. Arteminolides inhibited the farnesyl protein transferase with IC(50) values of 0.7-1 microM, while the regioisomers 5-7 were inactive. In addition, it was proved that the exocyclic double bond of sesquiterpene lactone did not affect the inhibitory activity of arteminolide. The effects of compound 2 on H-Ras processing and cellular growth in H-ras-transformed cells were also evaluated.
Lee
Seung-Ho
SH
Marine Natural Products Laboratory, Korea Ocean Research & Development Institute, P.O. Box 29 Ansan, Seoul 425-600, Republic of Korea.
Kim
Hyae-Kyeong
HK
Seo
Jeong-Min
JM
Kang
Hyun-Mi
HM
Kim
Jong Han
JH
Son
Kwang-Hee
KH
Lee
Heesoon
H
Kwon
Byoung-Mog
BM
Shin
Jongheon
J
Seo
Youngwan
Y
D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011905:Genes, ras / Q000235:genetics; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D017368:Protein Prenylation; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification*; D014166:Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007783:Lactones; D012717:Sesquiterpenes; C484914:arteminolide A; C484912:arteminolide B; C484913:arteminolide C; D014166:Transferases