CHEMICAL AND BIOLOGICAL PROPERTIES OF A NEW CIS-DIAMMINEPLATINUM(II) COMPLEX CONTAINING PARA-AMINOBENZOIC ACID AS AMINO LIGAND

In this paper we report on the synthesis, characterization and prelimi nary pharmacological evaluation of a new platinum(ll) complex obtained by reaction of cis-diamminedichloro-platinum(ll) (DDP) with para-amin obenzoic acid (PAPA). The structure of this platinum compound was defi ned by UV, IR, 1H-NMR and elemental analysis. DPAB tested in vitro and in vivo against P388 leukemic cells displayed good antiproliferative (IC50 values after 48 h exposure of cells = 3 mu g/ml) and antitumor a ctivity (T/C%=150). This compound also possesses desirable physical pr oper-ties, such as a good solubility and stability in aqueous media, a nd a low toxicity (LD50 > 1200 mg/kg body weight) combined with a mode rate nephrotoxic activity [plasma urea nitrogen (PUN) level: 36 +/- 8( SD) mg/100 ml]. DPAB was cleared from plasma ultrafiltrate (UF-plasma) very rapidly [clearance (CL), 55.3 mix min-1 x kg-1], showing a half- life of 13.6 min. Platinum exposure (AUG) in the kidney was 2.6 times greater than that found in UP-plasma. AUCS for liver; stomach and UF p lasma were similar, while the AUC value for the spleen was 1.7 times l ower than that of UF-plasma. These preliminary results seem to hold in terest for further preclinical evaluation of the biological activity b f this new platinum compound.