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 preliminary pharmacological evaluation of a new platinum (II) complex obtained by reaction of cis-diamminedichloroplatinum(II) (DDP) with para-aminobenzoic acid (PABA). The structure of this platinum compound was defined 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 micrograms/ml) and antitumor activity (T/C% = 150). This compound also possesses desirable physical properties, such as a good solubility and stability in aqueous media, and a low toxicity (LD50 > 1200 mg/kg body weight) combined with a moderate 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 ml x min-1 x kg-1], showing a half-life of 13.6 min. Platinum exposure (AUC) in the kidney was 2.6 times greater than that found in UF-plasma. AUCS for liver, stomach and UF-plasma were similar, while the AUC value for the spleen was 1.7 times lower than that of UF-plasma. These preliminary results seem to hold interest for further preclinical evaluation of the biological activity of this new platinum compound.
Parodi
B
B
Istitut di Analisi e Tecnologie Farmaecutiche, University of Genova, Italy.
Esposito
M
M
Viale
M
M
Cafaggi
S
S
Vannozzi
M
M
D010129:4-Aminobenzoic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D007202:Indicators and Reagents; D007668:Kidney / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity*; D012995:Solubility; D013053:Spectrophotometry; D014018:Tissue Distribution; D062366:para-Aminobenzoates
C095182:(4-carboxyphenylamine)diamminechloroplatinum(I); D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007202:Indicators and Reagents; D009944:Organoplatinum Compounds; D062366:para-Aminobenzoates; D010129:4-Aminobenzoic Acid