Репозиторий Университета

© 2017 Elsevier B.V. Two series of palladium(II) and platinum(II) complexes featuring esters of tetrazol-1-yl and tetrazol-5-ylacetic acids {trans-[PdCl2L2] and trans-[PtCl2L2], L = 5-methyl-1H-tetrazol-1-ylacetic acid and its ethyl, butyl, isobutyl esters (1–5); 2-R-2H-tetrazol-5-ylacetic acid and its ethyl esters, R = tBu, CH2CH2OH (6–10)} were synthesized and their binding to calf-thymus DNA (CT DNA) and bovine serum albumin (BSA) were studied by means of experimental (CD, UV, viscometry, fluorometric and electrophoretic techniques) and theoretical methods. According to the spectrophotometric data, the interaction of the metal complexes with CT DNA is observed. The significant increase of melting point of CT DNA in the presence of the metal complexes (ΔTm = 8–13 °C) indicates strong stabilization of the DNA helix. Electrophoretic studies demonstrate the ability of the metal complexes to interact with pBR322 plasmid DNA and to change its mobility. According to the data of the fluorescence quenching technique, binding with constants (Kbin) of Pd(II) complexes with BSA are in the range 0.83–4.12 × 105 L M−1. The molecular docking studies show the minor groove binding behavior of tetrazole-containing palladium(II) and platinum(II) complexes to DNA (ΔGbinding. −5.56 − −6.12 kcal/mol) and effective binding to BSA via the favored binding site Trp213 (ΔGbinding −7.2 − −7.56 kcal/mol). The complex trans-[PtCl2(2-tert-butyl-tetrazol-5-ylacetic acid)2] exhibited noticeable antiproliferative activity in two human cancer cell lines with IC50 values of 11.40 µM in HT-29 cells and 11.02 µM in MDA-MB-231 cell line.

© 2018, Slovak Academy of Sciences. All rights reserved. The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands – ethylenediamine; 1,2-diaminocyclohexane; 2,2’:6’,2’’-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.