New gold pincer-type complexes: synthesis,characterization, DNA binding studies andcytotoxicity
| Main Authors: | Radisavljević Snežana, Bratsos Ioannis, Scheurer Andreas, Korzekwa Jana, Masnikosa Romana, Tot Aleksandar, Gligorijević Nevenka, Radulović Siniša, Rilak Simović Ana |
|---|---|
| Format: | Article Journal |
| Bahasa: | eng |
| Terbitan: |
, 2018
|
| Subjects: | |
| Online Access: |
https://zenodo.org/record/4315346 |
Daftar Isi:
- With the aim of assessing whether Au(III) compounds with pincer type ligands might be utilized as poten-tial antitumor agents, three new monofunctional Au(III) complexes of the general formula [Au(N–N’–N)Cl]Cl2, whereN–N’–N= 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu,1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu,2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me2*L,3) were synthesized. All complexes were characterized byelemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry(MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied byUV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold centerremained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes1–3with guanine derivatives (i.e.guanosine (Guo) and guanosine-5’-monophosphate (5’-GMP)) and calfthymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed mod-erately different rate constants in their reactions with Guo, 5’-GMP and CT DNA, which can be explainedby the steric hindrance andσ-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment incomplexes2and3. The measured enthalpies and entropies of activation (ΔH≠>0,ΔS≠< 0) supported anassociative mechanism for the substitution process. The interaction of the newly synthesized complexes1–3with CT DNA was investigated by UV-Vis andfluorescence spectroscopy, and also by viscositymeasurements, which all indicated that complexes1–3bound to CT DNA with moderate binding affinity(Kb= 1.6–5.7 × 103M−1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes1–3interacted with DNAviaintercalation. Complex1reduced the cell survival of all the investigated celllines (A549, A375, and LS-174) with IC50values being up to 20 μM. We have shown that1induced pertur-bations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex1also affectedthe level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells withNAC (ROS scavenger) reversed the effect of1on their survival.
- This work is dedicated to the deceased Prof. Dr Živadin D. Bugarčić, a great scientist in the field of bio-inorganic reaction mechanisms, teacher and a real friend.