Interest in antimicrobial gold complexes originated from the work of Robert Koch at the end of 19th century, who demonstrated that potassium dicyanidoaurate(I), K[Au(CN)2], showed activity against Mycobacterium tuberculosis, a causative agent of tuberculosis. Subsequently, a large number of gold(I) and gold(III) complexes have been evaluated as possible antimicrobial agents against a broad spectrum of bacteria, fungi and parasites. The first part of the present review article summarizes the results achieved in the field of antibacterial and antifungal activity of gold(I) and gold(III) complexes. The represented gold(I) complexes have been divided into three distinct classes based on the type of coordinated ligand: (i) complexes with phosphine-type ligands, (ii) complexes with N-heterocyclic carbene ligands and (iii) various other gold(I) complexes, while the results related to the antibacterial and antifungal gold(III) complexes have been mainly focused on the organometallic-type of complexes. The second section of this article represents findings obtained from the evaluation of antimalarial activity of gold complexes against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum parasite. Antimalarial gold(I) and gold(III) complexes have been divided into the following classes, based on the nature of the coordinated ligand: (i) complexes with chloroquine and its derivatives, (ii) complexes with N-heterocyclic carbene ligands, (iii) complexes containing functionalised alkynes and (iv) thiosemicarbazonato ligands, as well as (v) other gold(I) and gold(III) complexes. In the last section of the review, gold(I) and gold(III) complexes have been reported to be potential agents against parasites that cause amoebiasis, leishmaniasis and trypanosomiasis. A systematic summary of these results could contribute to the future design of new gold(I) and gold(III) complexes as potential antimicrobial agents.

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Combination therapy may be applied in the case of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles to improve their antimicrobial activity and reduce toxic-side effects.

Copper(ii) complexes with aromatic nitrogen-containing heterocycles are a new class of quorum sensing inhibitors that attenuate virulence without a pronounced effect on the bacterial growth, thus offering a lower risk for resistance development.

Gold(iii) complexes with different l-histidine-containing dipeptides, [Au(Gly-l-His-N,N,N3)Cl]Cl·3HO (1a), [Au(Gly-l-His-N,N,N3)Cl]NO·1.25HO (1b), [Au(l-Ala-l-His-N,N,N3)Cl][AuCl]·HO (2a), [Au(l-Ala-l-His-N,N,N3)Cl]NO·2.5HO (2b), [Au(l-Val-l-His-N,N,N3)Cl]Cl·2HO (3), [Au(l-Leu-l-His-N,N,N3)Cl]Cl (4a) and [Au(l-Leu-l-His-N,N,N3)Cl][AuCl]·HO (4b), have been synthesized and structurally characterized by spectroscopic (H NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. The antimicrobial efficiency of these gold(iii) complexes, along with K[AuCl] and the corresponding dipeptides, was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi, displaying their moderate inhibiting activity. Moreover, the cytotoxic properties of the investigated complexes were assessed against the normal human lung fibroblast cell line (MRC5) and two human cancer, cervix (HeLa) and lung (A549) cell lines. None of the complexes exerted significant cytotoxic activity; nevertheless complexes that did show selectivity in terms of cancer vs. normal cell lines (2a/b and 4a/b) have been evaluated using zebrafish (Danio rerio) embryos for toxicity and antiangiogenic potential. Although the gold(iii) complexes achieved an antiangiogenic effect comparable to the known angiogenic inhibitors auranofin and sunitinib malate at 30-fold higher concentrations, they had no cardiovascular side effects, which commonly accompany auranofin and sunitinib malate treatment. Finally, binding of the gold(iii) complexes to the active sites of both human and bacterial (Escherichia coli) thioredoxin reductases (TrxRs) was demonstrated by conducting a molecular docking study, suggesting that the mechanism of biological action of these complexes can be associated with their interaction with the TrxR active site.

Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl(1,7-phen-κN7)] (1) and [AuCl(4,7-phen-κN4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89μM, while had low toxicity with LC value (the concentration inducing the lethal effect of 50% embryos) of 128μM. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.