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.