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Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro.
Biochem Pharmacol
November 2024
College of Veterinary Medicine, Shanxi Agricultural University, 030801 Taigu, Shanxi, China; Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, 030801 Taigu, Shanxi, China. Electronic address:
The emerging antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV-visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays.
View Article and Find Full Text PDFChloroxine inhibits pancreatic cancer progression through targeted antagonization of the PI3K/AKT/mTOR signaling pathway.
Clin Transl Oncol
April 2024
Department for Hepato-Biliary-Pancreatic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People's Republic of China.
Background: Patients with pancreatic cancer have a dismal prognosis due to tumor cell infiltration and metastasis. Many reports have documented that EMT and PI3K-AKT-mTOR axis control pancreatic cancer cell infiltration and metastasis. Chloroxine is an artificially synthesized antibacterial compound that demonstrated anti-pancreatic cancer effects in our previous drug-screening trial.
View Article and Find Full Text PDFBroad susceptibility of strains to 8-hydroxyquinolines and mechanisms of resistance.
mBio
August 2023
Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
The fungal pathogen represents a severe threat to hospitalized patients. Its resistance to multiple classes of antifungal drugs and ability to spread and resist decontamination in healthcare settings make it especially dangerous. We screened 1,990 clinically approved and late-stage investigational compounds for the potential to be repurposed as antifungal drugs targeting and narrowed our focus to five Food and Drug Administration (FDA)-approved compounds with inhibitory concentrations under 10 µM for and significantly lower toxicity to three human cell lines.
View Article and Find Full Text PDFInsight into the Mode of Action of 8-Hydroxyquinoline-Based Blockers on the Histamine Receptor 2.
Biosensors (Basel)
May 2023
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Histamine receptor 2 (HR) blockers are used to treat peptic ulcers and gastric reflux. Chlorquinaldol and chloroxine, which contain an 8-hydroxyquinoline (8HQ) core, have recently been identified as blocking HR. To gain insight into the mode of action of 8HQ-based blockers, here, we leverage an HR-based sensor in yeast to evaluate the role of key residues in the HR active site on histamine and 8HQ-based blocker binding.
View Article and Find Full Text PDFUnlabelled: The fungal pathogen represents a severe threat to hospitalized patients. Its resistance to multiple classes of antifungal drugs and ability to spread and resist decontamination in health-care settings make it especially dangerous. We screened 1,990 clinically approved and late-stage investigational compounds for the potential to be repurposed as antifungal drugs targeting and narrowed our focus to five FDA-approved compounds with inhibitory concentrations under 10 µM for and significantly lower toxicity to three human cell lines.
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