Michael E. Friedman , Paul Melius , Charles A. McAuliffe
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A proposed mechanism relating the antitumor behavior of cis-platinum amine complexes to their inhibition of a model enzyme
The twenty-four hour inhibition of m-malate dehydrogenase (E.C. 1.1.1.37)1 by various complexes of cis-platinum(II) and cis-platinum(IV) was measured as a function of the platinum concentration. It was observed that increased alkylation of the amine groups of Pt(II) and to a lesser degree of Pt(IV) decreased the activity consistently. It was also observed that the Pt(IV) analogues inhibit the enzyme to about an order of magnitude greater than the Pt(II) complexes. These phenomena will be interpreted.
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