Antitumor Agents 60. Maytansine, An Antileukemic Principle From Maytenus diversifolia

Journal of Natural Products
1982.0

Abstract

The genus Maytenus is known as the source of novel ansa macrolides including the potent tumor inhibitor maytansine (1) (1,2). Maytansine is currently undergoing Phase II clinical trials as an anticancer agent by the National Cancer Institute (3). The extreme scarcity (0.00002% yield) of maytansine from plant sources, coupled with its high (at the level of pg/kg) and wide (from 50-100-fold dosage) range of activity against mouse P-388 lymphocytic leukemia and other tumor systems (2) prompted our examination of a hitherto uninvestigated Formosan Maytenus diversifolia (4) for a possible better source of maytansine as well as other potent new antileukemic constituents of unusual structure. The spinescent shrub M. diversifolia (Gray) Hou [ = Gymnosporia diversifolia (Gray) Maxim., or Catha diversifolia A. Gray ex Maxim., or Celastrus diversifolia (Gray) Hemsl., or Celastrus wallichianus Sensu Hance] (Celastraceae) is known as "Pak-Tiong (Pei-Chung)" or "Tzu-Lou-Shih" (5) in Taiwan. The methanolic extract of the stems of M. diversifolia was found to show significant inhibitory activity in vivo against the P-388 lymphocytic leukemia growth in BDK mice (T/C = 180%) at 50 mg/kg/day, I.P. Subsequent bioassay-directed fractionation in P-388 in vivo (6) led to the conclusion that the most active component of this extract was maytansine (1). Maytansine was isolated in a better yield of 0.0000374% of the dried plant material compared to that reported previously (1).

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