Aleksandra M. Bondžić, Dragana D. Vasić Anićijević, Goran V. Janjić, Ivana Zeković, Tatjana Momić, Ana Vujačić Nikezić and Vesna M. Vasić* Pages 4742 - 4798 ( 57 )
Background: Gold-based complexes represent a new class of potential metallodrugs. Although their action mechanism is not entirely understood, it was shown that gold complexes inhibit some enzymes’ activities. Among them, Na,K-ATPase is emerging as an essential target for various anticancer drugs. The functionalization of nanoparticles by gold(III) complexes could facilitate their delivery into the cells and enable the following of their distribution in the target tissues.
Objective: The paper presents an overview of Na,K-ATPase interaction with representative and structurally related cytotoxic gold(III) complexes. The results obtained by the employment of theoretical methods (DFT and docking studies) combined with the experimental approach involving a variety of nanotechnology-base techniques (UV/Vis, Raman and fluorescence spectroscopy, CD, AFM, DLS) are discussed. Detailed information was obtained on the enzyme’s conformational and structural changes upon binding the gold(III) complexes. The experimentally determined reaction parameters (constants of dissociation and the reaction stoichiometry) were predicted theoretically.
Conclusion: The presented results offer further support to the view that Na,K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest.
Na,K-ATPase, gold(III) complexes, nanoparticles, functionalization, docking, DFT.
VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, Institute of Chemistry, Technology and Metallurgy, National Institute of thе Republic of Serbia, University of Belgrade, Njegoseva 16, Belgrade, VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade, VINCA Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, P.O. Box 522, 11000 Belgrade