Two key cathepsins, TgCPB and TgCPL, are targeted by the vinyl sulfone inhibitor K11777 in in vitro and in vivo models of toxoplasmosis

Autor: Juan D Chaparro, Uyen Phuong Tran, Grace Hwang, Ken Hirata, Rosa M. Andrade, Shara Cohn, James H. McKerrow, Sara B. T. Brenner, Timmy Cheng, Sharon L. Reed
Přispěvatelé: Ferreira, Marcelo U
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Embryology
Protozoan Proteins
lcsh:Medicine
Pharmacology
Biochemistry
Piperazines
Toxoplasma Gondii
Pathogenesis
Tosyl Compounds
Animal Cells
Heterocyclic Compounds
Medicine and Health Sciences
Sulfones
lcsh:Science
Connective Tissue Cells
Protozoans
Multidisciplinary
Antiparasitic Agents
Organic Compounds
Eukaryota
Proteases
Dipeptides
Enzymes
Chemistry
Infectious Diseases
5.1 Pharmaceuticals
Connective Tissue
Toxicity
Physical Sciences
Development of treatments and therapeutic interventions
Cellular Types
Anatomy
Toxoplasma
Toxoplasmosis
Research Article
Vinyl Compounds
General Science & Technology
Phenylalanine
030106 microbiology
Biology
Vaccine Related
03 medical and health sciences
In vivo
Parasite Groups
medicine
Parasitic Diseases
Animals
Humans
Cathepsin
Protozoan Infections
lcsh:R
Embryos
Organic Chemistry
Organisms
Chemical Compounds
Toxoplasma gondii
Biology and Life Sciences
Proteins
Cell Biology
Fibroblasts
medicine.disease
biology.organism_classification
Cathepsins
In vitro
Parasitic Protozoans
030104 developmental biology
Emerging Infectious Diseases
Biological Tissue
Enzymology
Tachyzoites
Acridines
lcsh:Q
Parasitology
Apicomplexa
Chickens
Developmental Biology
Zdroj: PLoS ONE
Chaparro, JD; Cheng, T; Tran, UP; Andrade, RM; Brenner, SBT; Hwang, G; et al.(2018). Two key cathepsins, TgCPB and TgCPL, are targeted by the vinyl sulfone inhibitor K11777 in in vitro and in vivo models of toxoplasmosis. PLOS ONE, 13(3). doi: 10.1371/journal.pone.0193982. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/6jk468f6
PLoS ONE, Vol 13, Iss 3, p e0193982 (2018)
PloS one, vol 13, iss 3
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0193982.
Popis: Although toxoplasmosis is one of the most common parasitic infections worldwide, therapeutic options remain limited. Cathepsins, proteases that play key roles in the pathogenesis of toxoplasmosis and many other protozoan infections, are important potential therapeutic targets. Because both TgCPB and TgCPL play a role in T. gondii invasion, we evaluated the efficacy of the potent, irreversible vinyl sulfone inhibitor, K11777 (N-methyl-piperazine-Phe-homoPhe-vinylsulfone-phenyl). The inhibitor's toxicity and pharmacokinetic profile have been well-studied because of its in vitro and in vivo activity against a number of parasites. We found that it inhibited both TgCPB (EC50 = 114 nM) and TgCPL (EC50 = 71 nM) in vitro. K11777 also inhibited invasion of human fibroblasts by RH tachyzoites by 71% (p = 0.003) and intracellular replication by >99% (p
Databáze: OpenAIRE
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