Isolation of a new vinca alkaloid from the leaves of Ervatamia microphylla as an inhibitor of ras functions.
A new vinca alkaloid was isolated from a chroloform extract of Ervatamia microphylla leaves as a potent inhibitor of ras functions. The structure of the new alkaloid was elucidated by spectroscopic analysis to be a dimer of aspidosperma-class indoles. The new inhibitor, named III-121C, induced normal morphology in K-ras(ts)-NRK cells at around 0.3 microgram/ml. It also inhibited DNA, RNA, and protein synthesis weakly at 0.3 microgram/ml. It inhibited the growth of K-ras(ts)-NRK cells with IC50s of 0.29, and 0.20 microgram/ml at 33 degrees C and 39 degrees C, respectively. III-121C is the first vinca alkaloid that inhibits ras functions.
Umezawa
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Ohse
T
T
Yamamoto
T
T
Koyano
T
T
Takahashi
Y
Y
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D011905:Genes, ras / Q000187:drug effects*; D007668:Kidney; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves; D051381:Rats; D014748:Vinca Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000199:Actins; D010936:Plant Extracts; D014748:Vinca Alkaloids