title: Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine: Synthesis, X-ray structure and biological activity evaluation.
abstract: To assess the potential cytostatic properties of Pt(II) complexes with 3-hydroxymethylpyridine (3-hmpy) as the only carrier ligand, novel cis-[PtCl2(3-hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2) have been prepared. Elemental analysis, FTIR spectroscopy, multinuclear NMR spectroscopy and X-ray crystallography were used to determine their structures. Based on the results obtained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and clonogenic assay on T24 human bladder carcinoma cells (T24), the most potent compound 2 was further tested for cytotoxicity in human ovarian carcinoma cell lines - cisplatin sensitive (IGROV 1) and its resistant subclone (IGROV 1/RDDP). The cytotoxicity of compound 2 in IGROV 1/RDDP is comparable to cisplatin. Furthermore, compound 2 induced severe conformational changes in plasmid DNA, which resulted in a delayed onset of apoptosis in T24 cells, and higher amounts of Pt in tumours and serum compared to cisplatin. In addition, in vivo antitumour effectiveness was comparable to that of cisplatin with a smaller reduction of animals' body weight, thus demonstrating that it is a promising transplatin analogue which deserves further studies.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia. Electronic address: sabina.grabner@fkkt.uni-lj.si.
authors.forename: Sabina
authors.initials: S
authors.lastname: Grabner
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Modec
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Bukovec
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Bukovec
authors.affiliation: Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Čemažar
authors.affiliation: Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia.
authors.forename: Simona
authors.initials: S
authors.lastname: Kranjc
authors.affiliation: Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Serša
authors.affiliation: Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Sčančar
mesh_terms: D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009540:Nicotinyl Alcohol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D010984:Platinum; D009540:Nicotinyl Alcohol
keywords: Apoptosis; In vivo test; Plasmid DNA; Platinum accumulation; Pt(II) complexes