Guanidine platinum(II) complexes
- Author(s)
- Anton A. Legin, Michael A. Jakupec, Nadezhda A. Bokach, Marina R. Tyan, Vadim Yu. Kukushkin, Bernhard K. Keppler
- Abstract
The novel guanidine compounds trans-[Pt(NH
2Me)
2{NH=C(NHMe)NR}
2](Cl)
2 (R = NEt
2 [7], NC
5H
10 [8]) (trans-7,8) were synthesized by the nucleophilic addition of methylamine to dialkylcyanamide ligands of the push-pull nitrile complexes trans-[PtCl
2(RCN)
2] (R = NEt
2, NC
5H
10). In vitro cytotoxicity tests conducted for the entire series of the guanidine complexes, i.e. trans-7,8, the neutral cis- or trans-[PtCl
2{NH=C(NH
2)R}
2] (cis-1-3 and trans-1-3) and the cationic cis- or trans-[Pt(NH
3)
2{NH=C(NH
2)R}
2](Cl)
2 (cis-4-6 and trans-4-6) (R = NMe
2 [1,4], NEt
2 [2,5], NC
5H
10 [3,6]) in two human cancer cell lines, CH1 (ovarian carcinoma) and SW480 (colon cancer), confirmed that the cytotoxicity of several trans-configured (trans-3,6) complexes is higher than that of cis-congeners (cis-3,6). Cellular platinum levels were analyzed by inductively coupled plasma mass spectrometry upon treatment of SW480 cells, revealing a dependence of cellular accumulation on the geometrical isomerism and the steric hindrance of the variable substituent R on the guanidine ligand. DNA interactions of selected guanidine complexes were studied in order to find hints for the possible reasons for their different activities. Changes induced to the electrophoretic mobility of a dsDNA plasmid confirmed the potency of the guanidine complexes (e.g. trans-1,3,5,6 and cis-1,3,4) to significantly alter DNA secondary structure, indicating DNA as a possible critical target of these compounds.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Saint Petersburg State University
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 133
- Pages
- 33-39
- No. of pages
- 7
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/j.jinorgbio.2013.12.007
- Publication date
- 04-2014
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research, 106023 Molecular biology
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/dbb50050-f75e-4ccb-a5b5-5141b460c137