![]() 6 Subsequently, a large number of gold( I) and gold( III) complexes were synthesized and showed remarkable antimicrobial activity against various bacterial and fungal species. 6 Interest in the antimicrobial activity of gold( I) and gold( III) complexes dates back to the discovery of Robert Koch at the end of the 19 th century, who found that potassium dicyanidoaurate( I), K, inhibited the growth of Mycobacterium tuberculosis, which is a causative agent of tuberculosis. The pharmacological properties of gold and its compounds have been known since antiquity, 11 and to date, gold compounds have been studied against the causative agents of various diseases, although they are currently used only for the treatment of rheumatoid arthritis. 9 Additionally, metal complexes can have different modes of action, which are often impossible to achieve with organic drugs, such as ligand exchange or release, formation of reactive oxygen species (ROS), redox activation and depletion of essential substrates. An important advantage of a medicinal use of metal complexes over organic drugs is that they have a versatile geometry, which may lead to a higher clinical success rate of metal complexes. Besides that, metal-based drugs are used to treat cancer, 5 rheumatoid arthritis and other inflammatory diseases, 6 bipolar 7 and gastrointestinal 8 disorders. Introduction The use of metals and metal compounds in medicine is diverse and includes fundamental wide-reaching medical problems such as bacterial and fungal, 1,2 viral 3 and parasitic 4 infections. These findings could be of importance for the development of novel gold( III)-based antivirulence therapeutic agents that attenuate virulence without pronounced effect on the growth of the pathogens, offering a lower risk for resistance development. Finally, complexes 5 and 6 significantly reduced the production of pyocyanin, a virulence factor in Pseudomonas aeruginosa controlled by quorum sensing, and increased cell survival after exposure to this bacterium. Gold( III) complexes 1–3 significantly reduced the amount of ergosterol in the cell membrane of Candida albicans at the subinhibitory concentration of 0.5 × MIC (minimal inhibitory concentration), while the corresponding imidazole ligands did not significantly affect the ergosterol content, indicating that the mechanism of action of the gold( III)–azole complexes is associated with inhibition of ergosterol biosynthesis. The complexes 4–7 and the corresponding antifungal azoles inhibited the growth of dermatophyte Microsporum canis at 50 and 25 μg mL −1. Moreover, gold( III) complexes 4–7 with clinically used antifungal agents clotrimazole, econazole, tioconazole and voriconazole, respectively, have, in most cases, enhanced antimicrobial effectiveness relative to the corresponding azoles, with the best improvement achieved after complexation of tioconazole ( 6) and voriconazole ( 7). In vitro antimicrobial assays showed that the complexation of inactive azoles, imidazole, 1-isopropylimidazole and 1-phenylimidazole, to the Au( III) ion led to complexes 1–3, respectively, with moderate activity against the investigated strains and low cytotoxicity on the human normal lung fibroblast cell line (MRC-5). In all complexes, the corresponding azole ligand is monodentately coordinated to the Au( III) via the imidazole or triazole nitrogen atom, while the remaining coordination sites are occupied by chloride anions leading to the square-planar arrangement. E-mail: a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold( III) complexes 1–7 of the general formula, where azole stands for imidazole (im, 1), 1-isopropylimidazole (ipim, 2), 1-phenylimidazole (phim, 3), clotrimazole (ctz, 4), econazole (ecz, 5), tioconazole (tcz, 6) and voriconazole (vcz, 7) were synthesized, characterized and biologically evaluated. ![]() Dr Zorana Đinđića 81, 18108 Niš, Serbia e Serbian Academy of Sciences and Arts, Knez Mihailova 35, 11000 Belgrade, Serbia. ![]() E-mail: d University of Niš, Faculty of Medicine, Department of Chemistry, Blvd. E-mail: c Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia. E-mail: b Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000, Ljubljana, Slovenia. * a a University of Kragujevac, Faculty of Science, Department of Chemistry, R. ![]() Dalton Trans., 2022, 51, 5322-5334 Clinically used antifungal azoles as ligands for gold( III) complexes: the influence of the Au( III) ion on the antimicrobial activity of the complex †
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