Interakcija bipiridinskih kompleksa zlata(III) i polioksovolframata sa Na+/K+-ATPazom i acetilholinesterazom

Abstract

U ovoj doktorskoj disertaciji ispitan je uticaj antitumorskih mononuklearnih i binuklearnih kompleksa zlata(III) (AubipyC, Aubipy(OH)2, Aupy(OAc)2, Auoxo6, Au2bipyC i Au2phen) na Na+/K+-ATPazu, kao i uticaj polioksometalata, 12- volframsilicijumove i 12-volframfosforne kiseline (WSiA i WPA) na acetilholinesterazu (AChE). Primenom različitih fizičkohemijskih metoda (UV/Vis i fluorescentna spektroskopija, cirkularni dihroizam, elektronska paramagnetna rezonantna (EPR) spektroskopija) u kombinaciji sa molekulskim modelovanjem, dobijen je detaljan uvid u njihovu interakciju na molekulskom nivou. Ispitivanjem uticaja ovih jedinjenja na antioksidativne enzime i na nivo malondialdehida, procenjeni su njihovi toksični potencijali, a merenjem učestalosti mikronukleusa i indeksa ćelijske proliferacije procenjeni su njihovi genotoksični i citotoksični efekti...

In this doctoral dissertation, the interaction of antitumor mononuclear and binuclear gold(III) complexes (AubipyC, Aubipy(OH)2, Aupy(OAc)2, Auoxo6, Au2bipyC and Au2phen) with Na+/K+-ATPas,e as well as the interaction of polioxotungstates, 12- tungstosilicic acid and 12-tungstophosphoric acid (WSiA and WPA), with acetylholinesterase have been investigated. Various spectroscopic methods (UV/Vis and fluorescent spectroscopy, circular dichroism, electron paramagnetic resonance (EPR) spectroscopy) in combination with docking studies were used in order to obtain detailed insight into their interaction on the molecular level. By investigating the influence of these compounds on the antioxidative enzymes and the level of malondialdehyde, their toxic potentials were evaluated. Furthermore, their genotoxic and cytotoxic effects were estimated by measuring the incidence of micronuclei and the cytokinesis-block proliferation index in human lymphocyte cultures...