Synthesis and antiproliferative activity of new carboplatin analogues

The aim of this study was to present the synthesis and characterization of two carboplatin analogues and to investigate their antiproliferative activity against human tumor cell lines.

The carboplatin analogues cis-1,2-propylendiammine (cyclobutane-1,1-dicarboxylato) platinum (II) (MD2), and cis-izobutylendiammine (cyclobutane-1,1-dicarboxylato)platinum (II) (MD3) were characterized by elemental analysis and (1)H-NMR-measurements. The compounds were tested for antiproliferative activity against the following human tumor cell lines: myelogenous leukemia K562, colon adenocarcinoma HT- 29, breast adenocarcinoma MCF-7, and human lung fetal fibroplast cell line MRC-5. The active substance of carboplatin (MD1) was used as reference compound. Cells were exposed to complexes for 24 h at concentrations ranging from 10(-3) to 10(-8)M. Growth inhibition was evaluated by the colorimetric SRB assay. The IC(50) value of each carboplatin compound was determined by median effects analysis.

Both carboplatin analogues induced dose-dependent growth inhibition of human tumor cell lines after 24 h of treatment. The MD3 analogue was 60-fold and the MD2 was 2-foild more active against K562 cell line compared to the referent compound. The activity of both analogues was comparable to the refernt compound against MCF-7 cell line. Colon adenocarcinoma cell line HT-29 was found to be 4-fold less sensitive to MD2 but equally sensitive to MD3 with respect to carboplatin referent compound. Both carboplatin and its analogues induced moderate cytotoxicity on MRC-5 cell line ranging from 25% (10(-7)M) to 46%(10(-3)M).

This study showed that the two novel carboplatin analogues inhibited human cell lines in a different manner depending on cell line. Carboplatin analogues were more active against human tumor cell lines than against human lung fibroplast cell line MRC-5.