Novel plant-derived tumor inhibitors and their mechanisms of action

The activity-directed isolation of new tumor inhibitors of plant origin has yielded many novel compounds with significant growth-inhibitory properties. A large proportion of the new compounds contain highly electrophilic functionalities and chemical and biochemical studies are yielding a growing body of evidence to support the view that these compounds may act by selective alkylation of growth-regulatory biologic macromolecules. The selectivity may result from many factors, among which are transport of the tumor inhibitor into the cell and the chemical nature and steric environment of the specific nucleophile to be alkylated. Model studies support the hypothesis that the inhibition of tumor growth by the new agents may be attributable to selective alkylation of key enzymes which control cell division.