0471954 - BFÚ 2017 RIV US eng J - Článek v odborném periodiku
Schmitt, F. - Donnelly, K. - Muenzner, J.K. - Rehm, T. - Novohradský, Vojtěch - Brabec, Viktor - Kašpárková, Jana - Albrecht, M. - Schobert, R. - Mueller, T.
Effects of histidin-2-ylidene vs. imidazol-2-ylidene ligands on the anticancer and antivascular activity of complexes of ruthenium, iridium, platinum, and gold.
Journal of Inorganic Biochemistry. Roč. 163, OCT2016 (2016), s. 221-228. ISSN 0162-0134. E-ISSN 1873-3344
Grant CEP: GA ČR(CZ) GA14-21053S
Institucionální podpora: RVO:68081707
Klíčová slova: n-heterocyclic carbene * human cancer-cells * metal-complexes
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.348, rok: 2016 ; AIS: 0.638, rok: 2016
DOI: https://doi.org/10.1016/j.jinorgbio.2016.07.021

Couples of N-heterocyclic carbene complexes of ruthenium, iridium, platinum, and gold, each differing only in the carbene ligand being either 1,3-dimethylimidazol-2-ylidene (IM) or 1,3-dimethyl-N-boc-O-methylhistidin-2-yl-idene (HIS), were assessed for their antiproliferative effect on seven cancer cell lines, their interaction with DNA, their cell cycle interference, and their vascular disrupting properties. In mTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays only the platinum complexes were cytotoxic at single-digit micromolar IC50 concentrations with the (HIS)Pt complex being on average twice as active as the (IM)Pt complex. The former was highly efficacious against cisplatin-resistant HT-29 colon carcinoma cells where the latter had no effect. Both Pt complexes were accumulated by cancer cells and bound to double-helical DNA equally well. Only the (HIS)Pt complex modified the electrophoretic mobility of circular DNA in vitro due to the HIS ligand causing greater morphological changes to the DNA. Both platinum complexes induced accumulation of 518A2 melanoma cells in G2/M and S phase of the cell cycle. A disruption of blood vessels in the chorioallantoic membrane of fertilized chicken eggs was observed for both platinum complexes and the (IM)gold complex. The (HIS)platinum complex was as active as cisplatin in tumor xenografted mice while being tolerated better. We found that the HIS ligand may augment the cytotoxicity of certain antitumoral metal fragments in two ways: by acting as a transmembrane carrier increasing the cellular accumulation of the complex, and by initiating a pronounced distortion and unwinding of DNA. We identified a new (HIS)platinum complex which was highly cytotoxic against cancer cells including cisplatin-resistant ones. (C) 2016 Elsevier Inc All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0269315