Clinically used antifungal azoles as ligands for gold(<scp>iii</scp>) complexes: the influence of the Au(<scp>iii</scp>) ion on the antimicrobial activity of the complex

Stevanović, Nevena Lj.; Kljun, Jakob; Aleksić, Ivana; Milivojević, Dušan; Veselinović, Aleksandar M.; Turel, Iztok; Djuran, Miloš I.; Nikodinovic-Runic, Jasmina; Glišić, Biljana Đ.

doi:10.1039/d2dt00411a

Cited by 12 publications

(10 citation statements)

References 79 publications

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“…Similar piano stool compounds [ 14 , 15 ] as well as iridium complexes with different scaffolds [ 16 , 17 , 18 , 19 ] were investigated by other groups with comparably promising results. Apart from iridium, gold, as a further example of a third-row transition metal, is popular and effective in antimicrobial research [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

et al. 2023

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In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics.

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Section: Introductionmentioning

confidence: 99%

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

et al. 2023

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Section: Methodsmentioning

confidence: 99%

“…In vitro cell infections assay with Human lung carcinoma cells (A549) obtained from the American Type Culture Collection (ATCC; Manassas, Virginia, USA) was performed according to previously published procedure, with minor modifications. 21 S. aureus NCTC 6571 was used as infectious agent, while treatment included the addition of subinhibitory (0.5 MIC and 0.75 MIC) and MIC values of 14a at the time of infection.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Antibiotic Potential of the Ambigol Cyanobacterial Natural Product Class and Simplified Synthetic Analogs

Milzarek,

Stevanovic,

Milivojevic

et al. 2023

ACS Infect. Dis.

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The ambigols are cyanobacterial natural products characterized by three polychlorinated aromatic building blocks connected by biaryl and biaryl ether bridges. All ambigols known to date possess promising biological activities. Most significantly, ambigol A was reported to have antibacterial activity against Gram-positive bacteria, such as Bacillus megaterium and B. subtilis. We established a diverse compound library for in-depth biological evaluation building on our previous bio-and total synthetic research on this natural product family. To explore the antimicrobial potential in detail and to determine initial structure−activity relationships of this product class, a large set of dimeric and trimeric compounds were screened against selected bacterial and Candida target strains. Our results reveal exceptional antibiotic activity of the ambigols, especially against challenging clinical isolates.

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“…Incorporating Au(III) into clinically approved antifungal azoles have been achieved via metalation of the imidazole (Chart ). These Au(III) complexes display antifungal activity in multiple Candida strains including albicans , glabrata , kusei , and auris in the submicromolar range. An asexual fungus, Microsporum canis , is highly prevalent worldwide that has high relapse rates and treatment failures could benefit from more efficacious antifungal agents such as gold-based antifungals.…”

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

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The gold drugs, gold sodium thiomalate (Myocrisin), aurothioglucose (Solganal), and the orally administered auranofin (Ridaura), are utilized in modern medicine for the treatment of inflammatory arthritis including rheumatoid and juvenile arthritis; however, new gold agents have been slow to enter the clinic. Repurposing of auranofin in different disease indications such as cancer, parasitic, and microbial infections in the clinic has provided impetus for the development of new gold complexes for biomedical applications based on unique mechanistic insights differentiated from auranofin. Various chemical methods for the preparation of physiologically stable gold complexes and associated mechanisms have been explored in biomedicine such as therapeutics or chemical probes. In this Review, we discuss the chemistry of next generation gold drugs, which encompasses oxidation states, geometry, ligands, coordination, and organometallic compounds for infectious diseases, cancer, inflammation, and as tools for chemical biology via gold–protein interactions. We will focus on the development of gold agents in biomedicine within the past decade. The Review provides readers with an accessible overview of the utility, development, and mechanism of action of gold-based small molecules to establish context and basis for the thriving resurgence of gold in medicine.

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Clinically used antifungal azoles as ligands for gold(iii) complexes: the influence of the Au(iii) ion on the antimicrobial activity of the complex

Abstract: In a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold(III) complexes 1 – 7 of the general formula [AuCl3(azole)], where azole stands for imidazole (im, 1), 1-isopropylimidazole (ipim, 2),...

Cited by 12 publications

References 79 publications

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents

Antibiotic Potential of the Ambigol Cyanobacterial Natural Product Class and Simplified Synthetic Analogs

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

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