Arteminolides B, C, and D, New Inhibitors of Farnesyl Protein Transferase from Artemisia argyi

• Published in: Journal of organic chemistry Vol. 67; no. 22; pp. 7670 - 7675
• Main Authors: LEE, Seung-Ho, KIM, Hyae-Kyeong, SEO, Jeong-Min, KANG, Hyun-Mi, KIM, Jong Han, SON, Kwang-Hee, LEE, Heesoon, KWON, Byoung-Mog, SHIN, Jongheon, SEO, Youngwan
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.11.2002; Amer Chemical Soc
• Subjects: Animals; Artemisia - chemistry; Biological and medical sciences; Chemistry; Chemistry, Organic; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General pharmacology; Genes, ras - genetics; Lactones - chemistry; Lactones - isolation & purification; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Molecular Conformation; Molecular Structure; NIH 3T3 Cells; Oxidation-Reduction; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Physical Sciences; Protein Prenylation; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Transferases - antagonists & inhibitors; Transferases - metabolism; Asia; Korea; CELLS; SYLVATICA; SESQUITERPENE LACTONES; Antineoplastic agent; Chemical analysis; Molecular structure; Enzyme; Pharmacognosy; Transferases; Enzyme inhibitor; Alcohol; Polycyclic compound; Lactone; 3T3-Cell line; NMR spectrometry; Farnesyl-diphosphate farnesyltransferase; In vitro; Plant origin; Isolation; Ras gene; Enone; Ethylenic compound
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo020299z

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 IC50 values of 0.7-1 muM, 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.