Identification of a Proteasome-Targeting Arylsulfonamide with Potential for the Treatment of Chagas’ Disease-Reference-Cited by-同舟云学术

Identification of a Proteasome-Targeting Arylsulfonamide with Potential for the Treatment of Chagas’ Disease

Published:2022-01-18 Issue:1 Volume:66 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Lima Marta L.¹,Tulloch Lindsay B.¹,Corpas-Lopez Victoriano¹,Carvalho Sandra¹,Wall Richard J.¹,Milne Rachel¹,Rico Eva¹,Patterson Stephen¹,Gilbert Ian H.,Moniz Sonia¹,MacLean Lorna²,Torrie Leah S.²,Morgillo Carmine²,Horn David¹^ORCID,Zuccotto Fabio²,Wyllie Susan¹^ORCID

Affiliation:

1. Division of Biological Chemistry and Drug Discovery, Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom

2. Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom

Abstract

Phenotypic screening identified an arylsulfonamide compound with activity against Trypanosoma cruzi , the causative agent of Chagas’ disease. Comprehensive mode of action studies revealed that this compound primarily targets the T. cruzi proteasome, binding at the interface between β4 and β5 subunits that catalyze chymotrypsin-like activity.

Funder

Wellcome Trust

The Royal Society

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01535-21

Reference43 articles.

1. WHO. 2021. Chagas disease fact sheet. World Health Organization Geneva Switzerland.

2. Research priorities for Chagas disease, human African trypanosomiasis, and leishmaniasis;WHO;World Health Organ Tech Rep Ser,2012