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Biomedical subjects

S M Kupchan

Publications and source records attributed to S M Kupchan.

At least 37 records · Page 2Linked to original sources

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.

Animals↗

Antimitotic activity of the potent tumor inhibitor maytansine.

Maytansine, at 6x10(-8)M, irreversibly inhibits cell division in eggs of sea urchins and clams. It causes the disappearance of a mitotic apparatus or prevents one from forming if added at early stages. Maytansine does not affect formation of the mitotic organizing center but does inhibit in vitro polymerization of tubulin. Maytansine and vincristine inhibit in vitro polymerization of tubulin at about the same concentrations, but vincristine is about 100 times less effective as an inhibitor of cleavage in marine eggs.

Animals↗

Mezerein: antileukemic principle isolated from Daphne mezereum L.

An alcohol-water extract of Daphne mezereum L., a plant widely used in folk medicine for treating cancers, showed antileukemic activity against the P-388 lymphocytic leukemia in mice. Systematic fractionation of the extract has led to isolation and characterization of mezerein as the principal antileukemic component.

Animals↗

Selective alkylation: a biomimetic reaction of the antileukemic triptolides?

The potent antileukemic plant principles triptolide and tripdiolide contain a characteristic hydrogen-bonded 9,11-epoxy-14beta-hydroxy system. They alkylate propanethiol in a process which involves opening of the epoxide function with neighboring hydroxyl assistance. The reaction may mimic the inhibition of tumor growth via selective alkylation of the thiol groups of key enzymes concerned with groth regulation.

Alkylating Agents↗