Cancer molecular biology and strategies for the design of cytotoxic gold(i) and gold(iii) complexes: a tutorial review

Abstract

This tutorial review highlights key principles underpinning the design of selected metallodrugs to target specific biological macromolecules (DNA and proteins). The review commences with a descriptive overview of the eukaryotic...

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…Gold complexes can interact with G-quadruplexes at different binding sites, and can inhibit telomerase by blocking enzyme-DNA binding or by preventing the formation of G-quadruplexes altogether. 248 4.2 Selenoenzymes as the potential targets of gold complexes and the TrxR-ROS-ERS-ICD axis as a promising strategy for the treatment of cancer TrxR, glutathione peroxidase (GPx), and iodothyronine deiodinase (ID) are common mammalian selenoenzymes and play a significant role in antioxidant defense. These enzymes consist of selenocysteine (Sec) residues at the active site, which has a dramatic catalytic advantage over Cys residues.…”

Current Developments of N-Heterocyclic Carbene Au(I)/Au(III) Complexes toward Cancer Treatment

“…Similarly, an increase in stability can also be achieved using chelated ligands with softer, more polarizable donor atoms such as [N,N-], [C,N-], [C,N,N-], or [N,C,N-] [ 20 , 22 ]. Reports of Au(I) anticancer complex candidates with diverse ligands such as thiolates, phosphates, NHCs, alkynyl, and thiourea can be found in various reviews [ 22 , 23 , 24 ]. However, the scope of this present review mainly focuses on N -heterocyclic carbene bearing compounds.…”

“…Furthermore, tumorigenesis can be also triggered by viruses (e.g., HPV), initiating complications into the cell cycle via oncogene insertion or faulty stimulation of transcription of these oncogenes [ 62 , 63 ]. More in depth information regarding the cancer mechanism and the role of Au(I)/Au(III) carbene complexes in cancer can be found in the recent reviews of van der Westhuizen et al, Zou et al, or Mora et al [ 22 , 24 , 64 ].…”

Gold(i) metallocyclophosphazenes with antibacterial potency and antitumor efficacy. Synergistic antibacterial action of a heterometallic gold and silver-cyclophosphazene

“…Over the last 10-15 years considerable research has focused on the potential anticancer properties of gold complexes leading to very promising experimental drugs, not only in terms of their strong antiproliferation potency but also because of the variety of ligands that can be attached to the metal centres in various oxidation states, which in turn allows one to tune the cytotoxic effects with reduced side effects. 25 Auranofin, which was first approved in 1985 as an orally bioavailable antirheumatic drug, is currently one of the only three gold complexes approved for clinical use, which together with another Au(I) complex, myochrysine, are currently undergoing clinical trials as anticancer drugs. 26,27 Several reviews on this topic have recently appeared.…”

“…26,27 Several reviews on this topic have recently appeared. 25,[28][29][30][31][32] These surveys indicate that the stability of the ligands coordinated to the metal centre is a critical issue for the design of gold-based drugs. Thus, in the case of gold(I), ligands with relatively high bond dissociation energies, such as phosphanes, 20,33 carbenes 19,30 or alkynes, 18,34,35 are privileged moieties.…”