Synthesis and antiproliferative activity of new carboplatin analogues.

Abstract

PURPOSE:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: V Kojić, G Bogdanović, D Jakimov, I M Duran
• Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology (J BUON) 2005 Oct-Dec Vol. 10 Issue 4 Pg. 541-6 ISSN: 1107-0625 [Print] Cyprus
• PMID: 17357214 (Publication Type: Journal Article)