Evaluation of in vitro cytotoxicity of 6-benzylaminopurine carboplatin derivatives against human cancer cell lines and primary human hepatocytes.

Abstract

A series of seven platinum(II) cyclobutane-1,1-dicarboxylato (cbdc) complexes {[Pt(cbdc)(L(n))(2)], 1-7}, derived from carboplatin by a substitution of two NH(3) molecules for two 2,6,9-trisubstituted 6-benzylaminopurine-based N-donor ligands (L(n)), was studied by the MTT assay for their in vitro cytotoxic activity against seven human cancer cell lines, i.e. lung carcinoma (A549), cervix epithelioid carcinoma (HeLa), osteosarcoma (HOS), malignant melanoma (G361), breast adenocarcinoma (MCF7), ovarian carcinoma (A2780) and its cisplatin-resistant analogue (A2780cis), and against two primary cultures of human hepatocytes (LH31 and LH32). The prepared complexes were cytotoxic against several cancer cells, in some cases even more than cisplatin. The best results were achieved for complexes 1 (IC(50)=17.4 ± 2.0 μM) and 2 (IC(50)=14.8 ± 2.1 μΜ) against HOS cells, 1 (IC(50)=15.1 ± 6.8 μM), 2 (IC(50)=13.6 ± 5.2 μM) and 6 (IC(50)=19.0 ± 6.6 μM) against MCF7, 6 (IC(50)=6.4 ± 0.1 μM) against A2780, and 1-6 (IC(50)=15.6 ± 4.0, 12.9 ± 3.7, 15.8 ± 3.8, 16.6 ± 5.5, 22.1 ± 2.5, and 5.6 ± 1.7 μM, respectively) against A2780cis. Viability of human hepatocytes was not declined by the tested complexes up to the concentration of 50 μM (for 1, 3-7) and 20 μM (for 2; caused by lower solubility of this complex).

• Authors: Zdeněk Dvořák, Pavel Starha, Zdeněk Trávníček
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 25 Issue 3 Pg. 652-6 (Apr 2011) ISSN: 1879-3177 [Electronic] England
• PMID: 21232594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzyl Compounds
• Organoplatinum Compounds
• Purines
• Oxaliplatin
• Carboplatin
• benzylaminopurine
• Kinetin
• Cisplatin

Topics

• Adult
• Antineoplastic Agents (pharmacology)
• Benzyl Compounds
• Carboplatin (analogs & derivatives, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Hepatocytes (drug effects, metabolism, pathology)
• Humans
• Kinetin (chemistry, pharmacology)
• Male
• Neoplasms (drug therapy, metabolism, pathology)
• Organoplatinum Compounds (chemical synthesis, pharmacology)
• Oxaliplatin
• Purines