title: 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.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Cell Biology and Genetics, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic. moulin@email.cz
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
authors.forename: Pavel
authors.initials: P
authors.lastname: Starha
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001593:Benzyl Compounds; D016190:Carboplatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007701:Kinetin / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D000077150:Oxaliplatin; D011687:Purines
chemical_list: D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D009944:Organoplatinum Compounds; D011687:Purines; D000077150:Oxaliplatin; D016190:Carboplatin; C480551:benzylaminopurine; D007701:Kinetin; D002945:Cisplatin