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The quadrivalent second-generation platinum complex iproplatin and an in vivo divalent metabolite of iproplatin, cis-dichloro-bis-isopropylamine platinum (CIP) were tested for binding to DNA in vitro. DNA binding was determined according to radioactivity measured using [14C]-iproplatin and [14C]-CIP and also by platinum content. Results indicate that (a) iproplatin shows negligible binding to DNA, (b) CIP binds to DNA in a time-dependent fashion, and (c) the isopropylamine ligand is intact when CIP is bound to DNA. Glutathione (GSH) inhibits the binding of CIP to DNA, possibly by inhibiting binding to DNA of the aquated form of CIP.
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