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

Gascón, Elena; Otal, Isabel; Maisanaba, Sara; Llana-Ruiz-Cabello, María; Valero, Eva; Repetto, Guillermo; Jones, Peter G.; Oriol, Luis; Jiménez, Josefina

doi:10.1039/d2dt01963a

Cited by 11 publications

(2 citation statements)

References 114 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The chemical and physical properties of cyclotriphosphazenes change with the nature of substituted side groups. Therefore, it is possible to design materials with special properties such as biological active molecules [15][16][17][18][19], sensor molecules [20,21], liquid crystal molecules [22,23]. Also, N-heterocyclic-based cyclophosphazene ligands supply a rich coordination chemistry via multiple N-donor atoms [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Ag(I) and Hg(II) Coordination Polymers Decorated from Fully Benzimidazole Substituted Cyclotriphosphazene Ligand and Adsorption Behaviour Against Methylene Blue

Pendar,

Duyar,

Zorlu

et al. 2024

J Inorg Organomet Polym

View full text Add to dashboard Cite

Herein, we reported new two coordination polymers, {[Ag(L)](CH 3 PhSO 3 )](CH 3 CN) 4 } n (cp-1) and {[Hg(L)](Cl 2 )] (CH 3 CN) 2 } n (cp-2), were synthesized from hexapodal benzimidazole substituted cyclotriphosphazene, (L). L was characterised by 1 H NMR, 31 P NMR and mass analysis. Structure of each isolated compounds were determined by single crystal X-ray crystallography. In cp-1, L has a κ 3 N coordination mode by connecting three Ag(I) ions to constitute a 2D coordination framework whereas the ligand in cp-2 displays κ 2 N coordination mode via linking four Hg(II) ions together to create a 1D coordination polymer. Topologically, cp-1 has a 3-connected uninodal net having the point symbol {4.8 2 }. Dye adsorption studies of coordination polymers was performed out using UV-Vis. absorption spectroscopy. Adsorption experiments show that cp-1 and cp-2 removes the cationic methylene blue (MB) from water but shows no adsorption behaviour toward the anionic methyl orange (MO) and tartrazine (E102).

show abstract

An organometallic hybrid antibiotic of metronidazole with a Gold(I) N-Heterocyclic Carbene overcomes metronidazole resistance in Clostridioides difficile

Büssing,

Bublitz,

Karge

et al. 2024

J Biol Inorg Chem

View full text Add to dashboard Cite

Antimicrobial resistance (AMR) has been emerging as a major global health threat and calls for the development of novel drug candidates. Metal complexes have been demonstrating high efficiency as antibacterial agents that differ substantially from the established types of antibiotics in their chemical structures and their mechanism of action. One strategy to exploit this potential is the design of metal-based hybrid organometallics that consist of an established antibiotic and a metal-based warhead that contributes an additional mechanism of action different from that of the parent antibiotic. In this communication, we describe the organometallic hybrid antibiotic 2c, in which the drug metronidazole is connected to a gold(I) N-heterocyclic carbene warhead that inhibits bacterial thioredoxin reductase (TrxR). Metronidazole can be used for the treatment with the obligatory anaerobic pathogen Clostridioides difficile (C. difficile), however, resistance to the drug hampers its clinical success. The gold organometallic conjugate 2c was an efficient inhibitor of TrxR and it was inactive or showed only minor effects against eucaryotic cells and bacteria grown under aerobic conditions. In contrast, a strong antibacterial effect was observed against both metronidazole-sensitive and -resistant strains of C. difficile. This report presents a proof-of-concept that the design of metal-based hybrid antibiotics can be a viable approach to efficiently tackle AMR. Graphical abstract A metronidazole-gold hybrid metalloantibiotic with high efficacy against resistant C. difficile

show abstract

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

Abstract: One of the most important uses of phosphazenes today involves its biomedical applications. They can also be used as scaffolds for the design and construction of a variety of ligands...

Cited by 11 publications

References 114 publications

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

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

Ag(I) and Hg(II) Coordination Polymers Decorated from Fully Benzimidazole Substituted Cyclotriphosphazene Ligand and Adsorption Behaviour Against Methylene Blue

An organometallic hybrid antibiotic of metronidazole with a Gold(I) N-Heterocyclic Carbene overcomes metronidazole resistance in Clostridioides difficile

Contact Info

Product

Resources

About