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: Sabina Grabner, Barbara Modec, Nataša Bukovec, Peter Bukovec, Maja Čemažar, Simona Kranjc, Gregor Serša, Janez Sčančar
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 161 Pg. 40-51 (08 2016) ISSN: 1873-3344 [Electronic] United States
• PMID: 27189143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Cytotoxins
• Platinum
• Nicotinyl Alcohol

Topics

• Cell Line, Tumor
• Crystallography, X-Ray
• Cytotoxins (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Nicotinyl Alcohol (chemical synthesis, chemistry, pharmacology)
• Platinum (chemistry, pharmacology)