The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.
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http://dx.doi.org/10.1002/cmdc.202100342 | DOI Listing |
J Am Chem Soc
January 2025
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.
Effective delivery and controlled release of metallo-prodrugs with sustained activation and rapid response feed the needs of precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding and extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy of newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) with their photosensitization character to augment the mitochondrial release of Au(I) in tumors.
View Article and Find Full Text PDFJ Med Chem
January 2025
Sorbonne Université, CNRS Institut Parisien de Chimie Moléculaire, IPCM, F-75005 Paris, France.
Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) -heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex bearing a 4-CF-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. was able to induce cell apoptosis but had no effect on the cell cycle.
View Article and Find Full Text PDFPharmaceutics
December 2024
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
The therapeutic management of melanoma, the most aggressive form of skin cancer, remains challenging. In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved platinum-based drug and, based on its success, other metals (e.
View Article and Find Full Text PDFNat Commun
January 2025
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China.
Luminescent gold(I) compounds have attracted intensive attention due to anticipated strong spin-orbit coupling (SOC) resulting from heavy atom effect of gold atoms. However, some mononuclear gold(I) compounds are barely satisfactory. Here, we unveil that low participation of gold in transition-related orbitals, caused by 6s-π symmetry mismatch, is the cause of low SOCs in monogold(I) compounds.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Instituto de Biologia, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo, Brazil. Electronic address:
Leishmaniasis is one of the most important neglected diseases, classically characterized by three clinical forms that if left untreated can lead to skin lesions, lifelong scarring, or death depending on the parasite species. Unfortunately, treatment is unsatisfactory and the search for an improved therapy has been a priority. Gold compounds have emerged as promising candidates and among them, Au(I)bis-N-heterocyclic carbene (Au(BzTMX)) has stood out.
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