Antitumor and DNA-binding properties of a group of oligomeric complexes of platinum(II) and platinum(IV)

Abstract

The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-PtII(X)2(mu-OH)]2(NO3)2, where X is NH3, NH2CH2CH3, and NH2CH(CH3)2, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-PtII-(NH3)2Cl2. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-PtII(RR-DACH)(mu-OH)]3(NO3)3, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.

Electrophilic Substitution of (Diamine)tetrahydroxoplatinum(IV) with Carboxylic Anhydrides. Synthesis and Characterization of (Diamine)platinum(IV) Complexes of Mixed Carboxylates

“…The procedure was the same as described for 2 except for the quantities of pivalic (609 µL, 3 mmol) and acetic anhydrides (110 µL, 1 mmol). The product was obtained as a mixture of two stereoisomers, (dach)Pt(OPiv)3(OAc) ax (7) and (dach)Pt(OPiv)3(OAc) eq (8). Compound 7 was separated by recrystallization in a solvent pair of acetone and water.…”

“…Six-coordinate (diamine)platinum(IV) complexes have been of great interests − because of their potential applicability as oral anticancer drugs, as was exemplified by JM216, which has undergone extensive clinical trials. Lipophilicity and water solubility are important physicochemical properties for gastrointestinal absorption of drugs.…”