Platinum-Amine Compounds: Importance of the Labile and Inert Ligands for Their Pharmacological Activities Toward L1210 Leukemia Cells2

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Abstract
A series of Pt-amine compounds was assayed for their ability to inhibit the growth of cultured L1210 leukemia cells [median inhibitory dose (ID50)], their toxicity in mice [highest nonlethal dose in healthy mice (LD0)], their antitumor activity against leukemia L1210 cells grafted intraperitoneally into mice [mean survival of treated leukemic mice:mean survival of untreated leukemic mice (T/C)], and the ability to hydrolyze their labile ligands in vitro [hydrolysis half-time (t½)]. All Pt compounds exhibiting antitumor activity had a pair of labile ligands in the cis geometry with different charges, and the leaving groups had a wide range of hydrolysis rates. Among the compounds that showed antitumor activity, ID50 depended more on the inert ligands than on the labile ligands and was correlated with T/C. A relationship between LD0 and t½ was verified in the series of cis-Pt(II) compounds with the exception of the oxalate derivatives. Pt(II) and Pt(IV) compounds exhibited similar ID50, LD0 and T/C.