Anticancer and antibacterial properties of trinuclear Cu(I), Ag(I) and Au(I) macrocyclic NHC/urea complexes

Jakob, Christian; Muñoz, Angela Weigert; Schlagintweit, Jonas F.; Weiß, Vanessa; Reich, Robert M.; Sieber, Stephan A.; Correia, João D. G.; Kühn, Fritz E.

doi:10.1016/j.jorganchem.2020.121643

Cited by 36 publications

(19 citation statements)

References 56 publications

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“…In recent years, medicinal applications of gold(I)-NHC complexes focused mostly on their anticancer activity (Samanta et al, 2015;Mora et al, 2019;Patil et al, 2020;Behera et al, 2021;Guarra et al, 2021). In contrast, notably fewer contributions describing significant antimicrobial activities have been reported (Roymahapatra et al, 2012;Samanta et al, 2013;Büssing et al, 2021;Hussaini et al, 2021;Jakob et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria

et al. 2022

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The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 μM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents.

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Section: Introductionmentioning

confidence: 99%

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria

et al. 2022

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“…[7,8] The antibacterial activity of gold NHC biscarbene complexes was also decreased or lost when the organometallics were incorporated in macrocyclic structures. [11] Here we report on the extension of our efforts in developing antibacterial monocarbene gold NHC complexes by comparing a series of (NHC)Au(I)Cl complexes with the respective gold(III) derivatives of the type (NHC)Au(III)Cl 3 . The structures of the carbene ligands contain ethyl groups on the nitrogen side chains, in continuation of our previous work with this type of complexes.…”

Section: Introductionmentioning

confidence: 99%

Gold(I) and Gold(III) N‐Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

et al. 2021

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A series of (NHC)Au(I)Cl monocarbene complexes and their gold(III) analogues (NHC)Au(III)Cl3 were prepared and investigated as antibacterial agents and inhibitors of bacterial TrxR. The complexes showed stronger antibacterial effects against the Gram‐positive MRSA and E. faecium strains than against several Gram‐negative bacteria. All complexes were efficient inhibitors of bacterial thioredoxin reductase, indicating that inhibition of this enzyme might be involved in their mechanism of action. The efficacy of gold(I) and gold(III) analogues was comparable in most of the assays. The cytotoxicity of the gold NHC compounds against cancer and human cells was overall weaker than the activity against the Gram‐positive bacteria, suggesting that their optimization as antibacterials warrants further investigation.

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“…In another study novel trinuclear macrocyclic copper (I), silver(I) ( 51 ), and gold(I) NHC complexes bearing a cyclic urea moiety were synthesized and evaluated by their antibacterial and cytotoxic activities by Jakob and co‐workers (Figure 15) (Jakob et al, 2021). Cytotoxic activity of complexes was screened against human cervix carcinoma cells (HeLa) and human breast cancer cells (MCF‐7).…”

Section: Silver (Ag)mentioning

confidence: 99%

“…IC 50 values of the complex 51 were found as 3.61 ± 1.04, and 3.03 ± 1.06 μM for HeLa, and MCF‐7, respectively. Complex 51 showed better cytotoxic activity than the reference drug cisplatin with IC 50 values of 39.9 ± 4.6 (11.05‐fold), and 18.1 ± 5.1 (5.97‐fold) μM for HeLa, and MCF‐7, respectively (Jakob et al, 2021).…”

Section: Silver (Ag)mentioning

confidence: 99%

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Silver(I)‐N‐heterocyclic carbene complexes challenge cancer; evaluation of their anticancer properties and in silico studies

Şahin‐Bölükbaşı

Cantürk-Kılıçkaya

Kılıçkaya

2021

Drug Development Research

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Because of the continuous need for efficient therapeutic agents against various kinds of cancers and infectious diseases, the pharmaceutical industry has to find new candidates and strategies to develop novel and efficient drugs. They increasingly use computational tools in R&D stages for screening extensive sets of drug candidates before starting pre‐clinical and clinical trials. N‐Heterocyclic carbenes (NHCs) can be evaluated as good drug candidates because they offer both anti‐cancer and anti‐inflammatory features with their general low‐toxicity profiles. To date, different kinds of NHCs (Cu, Co, Ni, Au, Ag, Ru, etc.) have been synthesized and their therapeutic uses has been shown. Here, we have reviewed the recent studies focused on Ag(I)‐NHC complexes and their anti‐cancer activities. Also, existing examples of the usage of density functional theory and structure–activity relationship have been evaluated.

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Anticancer and antibacterial properties of trinuclear Cu(I), Ag(I) and Au(I) macrocyclic NHC/urea complexes

Cited by 36 publications

References 56 publications

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria

A C∧S-Cyclometallated Gold(III) Complex as a Novel Antibacterial Candidate Against Drug-Resistant Bacteria

Gold(I) and Gold(III) N‐Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

Silver(I)‐N‐heterocyclic carbene complexes challenge cancer; evaluation of their anticancer properties and in silico studies

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