Synthesis of a new platinum(II) complex: anticancer activity and nephrotoxicity in vitro.
New mixed dithiocarbamate-amino Pt(II) complex ([Pt(ESDT)(Py)Cl]) has been recently synthesised with the aim to produce potential anticancer drug able to conjugate cytostatic activity with lack of nephrotoxicity. This complex contains: (1) an amino ligand; (2) a good leaving group (halide); and (3) an S-containing chelating agent potentially able to protect the metal centre from its interaction with S-containing protein-legating sites that are believed to be at the basis of the nephrotoxicity of Pt(II)-based drugs. This complex has been found to be effective as an antiproliferative agent (more active than cis-platin) towards a normal human adenocarcinoma cell line and the corresponding cis-platin-resistant C13 strain. Toxicity tests on the kidney were performed by means of a renal cortical slice model. The slices, prepared with a Brendel-Vitron slicer, were incubated with different doses (0.125-5.0 x 10(-4) M, final concentration) of [Pt(ESDT)(Py)Cl] or cis-platin dissolved in methyl sulphoxide. The platinum(II) complex showed very low renal cytotoxicity as compared with cis-platin; in particular, lipid peroxidation induced by cis-platin appeared about five-fold higher than that induced by [Pt(ESDT)(Py)Cl]. In conclusion, besides being less toxic for the kidney, the results showed that the new synthesised platinum(II) complex appeared in vitro more effective than cis-platin when tested on sensitive and resistant cis-platin tumour cell lines.
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
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Marzano
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Trevisan
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Giovagnini
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Fregona
D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D017671:Platinum Compounds / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D013859:Thiocarbamates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D013859:Thiocarbamates; D002945:Cisplatin