Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.

Autor: Petukhova VZ; Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Aboagye SY; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Ardini M; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Lullo RP; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Fata F; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Byrne ME; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Gabriele F; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Martin LM; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Harding LNM; Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Gone V; UICentre, Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Dangi B; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Lantvit DD; UICentre, Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Nikolic D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Ippoliti R; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy., Effantin G; University of Grenoble Alpes, CEA, CNRS, IBS, F-38000, Grenoble, France., Ling WL; University of Grenoble Alpes, CEA, CNRS, IBS, F-38000, Grenoble, France., Johnson JJ; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA., Thatcher GRJ; Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ, USA., Angelucci F; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. francesco.angelucci@univaq.it., Williams DL; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA. david_williams@rush.edu., Petukhov PA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. pap4@uic.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 22; Vol. 14 (1), pp. 3737. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1038/s41467-023-39444-y
Abstrakt: Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.
(© 2023. The Author(s).)
Databáze: MEDLINE
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