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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

General Review Article

Na, K-ATPase as a Biological Target for Gold(III) Complexes: A Theoretical and Experimental Approach

Author(s): Aleksandra M. Bondžić, Dragana D. Vasić Anićijević, Goran V. Janjić, Ivana Zeković, Tatjana Momić, Ana Vujačić Nikezić and Vesna M. Vasić*

Volume 28, Issue 23, 2021

Published on: 01 January, 2021

Page: [4742 - 4798] Pages: 57

DOI: 10.2174/0929867328999210101233801

Price: $65

Abstract

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.

Keywords: Na, K-ATPase, gold(III) complexes, nanoparticles, functionalization, docking, DFT.


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