8‐Hydroxyquinolines are bactericidal against <scp><i>Mycobacterium tuberculosis</i></scp>

Odingo, Joshua; Early, Julie V.; Smith, Julie; Johnson, James; Bailey, Mai A.; Files, Megan; Guzman, Junitta; Ollinger, Juliane; Korkegian, Aaron; Kumar, Anuradha; Ovechkina, Yulia; Parish, Tanya

doi:10.1002/ddr.21531

Cited by 19 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been demonstrated that the cloxyquin exhibited bactericidal activity against replicating M . tuberculosis (Odingo et al, ) The present study showed that cloxyquin ( 2 ) displayed the similar values of MIC and MBC against the MSSA and MRSA strains (Table ). It was suggested that cloxyquin has the iron chelating property to compete with the essential nutrient of the microorganisms (Boda, Pandit, Garai, Pal, & Basu, ).…”

Section: Discussionsupporting

confidence: 62%

Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Cherdtrakulkiat

Worachartcheewan

Tantimavanich

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

Methicillin‐resistant Staphylococcus aureus (MRSA) infection has been considered to be one of global health problems due to limited classes of effective antimicrobial drugs. Herein, 8‐hydroxyquinoline (8HQ) and its derivatives (1‐7) were investigated for their anti‐MRSA and antioxidant activities. Cloxyquin (2), a halogenated 8HQ, exerted the highest antimicrobial activity (MIC50 ≤ 5.57 μM) with high safety index, whereas an amino‐derivative 7 showed the strongest antioxidant activity. Additionally, quantitative structure‐activity relationship (QSAR) study demonstrated that mass, polarizability, topological charge, and van der Waals volume are essential properties governing the anti‐MRSA activity. Taken together, cloxyquin was highlighted as a promising compound for further development as a novel anti‐MRSA agent. QSAR findings would also benefit for further rational design of novel 8HQ‐based compounds to combat the MRSA resistance.

show abstract

Section: Discussionsupporting

confidence: 62%

Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Cherdtrakulkiat

Worachartcheewan

Tantimavanich

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…Compounds were tested for cytotoxicity against HepG2 cells as previously described. 48 , 69 , 70 Briefly, cells were exposed to compounds for 48–72 h, and viability was measured using CellTiter-Glo (Promega).…”

Section: Methodsmentioning

confidence: 99%

Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions

et al. 2022

Self Cite

View full text Add to dashboard Cite

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.

show abstract

“…High nitroxoline concentrations in urine and prostate tissue can be achieved with oral therapy compared to lower systemic concentrations ( Dufour and Bollack, 1979 ; Mrhar et al, 1979 ; Wijma et al, 2018 ). Activity against some mycobacterial quality control strains ( Mycobacterium bovis BCG ATCC 35734 and M. tuberculosis H37rv) has been demonstrated ( Odingo et al, 2019 ; Shah et al, 2016 ; Murugasu-Oei and Dick, 2001 ) yet data on clinical isolates, especially with respect to otherwise drug resistant MTB are lacking. In this study, we therefore assessed nitroxoline MICs of clinically isolated mycobacteria including MDR-TB isolates to investigate repurposing of nitroxoline for mycobacterial infections in the era of antimicrobial resistance.…”

Section: Introductionmentioning

confidence: 99%

In vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis

et al. 2022

View full text Add to dashboard Cite

Antimicrobial treatment options for mycobacterial infections are limited due to intrinsic resistance and the emergence of acquired resistance in Mycobacterium tuberculosis. Isolates resisting first- and second line drugs are raising concerns about untreatable infections and make the development of new therapeutic strategies more pressing. Nitroxoline is an old oral antimicrobial that is currently repurposed for the treatment of urinary tract infection (UTI). In this study, we report the in vitro activity of nitroxoline against 18 clinical isolates of M. tuberculosis complex (MTBC) (M. tuberculosis N = 16, M. bovis BCG N = 1, M. bovis sp. bovis N = 1). Since nitroxoline achieves high concentrations in the urinary tract, we included all MTBC-isolates from urinary samples sent to our laboratory between 2008 and 2021 (University Hospital of Cologne, Germany). Isolates from other sources (N = 7/18) were added for higher sample size and for inclusion of drug-resistant M. tuberculosis isolates (N = 4/18). Based on our clinical routine the fluorescence-based liquid media system BACTEC MGIT 960 was used for susceptibility testing of nitroxoline and mainstay antitubercular drugs. Nitroxoline yielded a MIC90 of 4 mg/L for MTBC. In all M. tuberculosis isolates nitroxoline MICs were at least two twofold dilutions below the current EUCAST susceptibility breakpoint of ≤16 mg/L (limited to E. coli and uncomplicated UTI). In vitro activity of nitroxoline can be considered excellent, even in multidrug-resistant isolates. Future studies with in vivo models should evaluate a potential role of nitroxoline in the treatment of tuberculosis in the era of drug resistance.

show abstract

8‐Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis

Cited by 19 publications

References 33 publications

Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions

In vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis

Contact Info

Product

Resources

About