RRC ID 63900
著者 Han Y, Adeyemi OS, Kabir MHB, Kato K.
タイトル Screening of compound libraries for inhibitors of Toxoplasma growth and invasion.
ジャーナル Parasitol Res
Abstract Toxoplasma gondii can infect virtually all warm-blooded animals, including humans. It can differentiate between rapidly replicating tachyzoites that cause acute infection and slowly growing bradyzoites in tissue cysts. Treatment options for toxoplasmosis are challenging because current therapies cannot eradicate the latent T. gondii infection that is mainly caused by the bradyzoite forms. Accordingly, recurrence of infection is a problem for immunocompromised patients and congenitally infected patients. Protein kinases have been widely studied in eukaryotic cells, and while little is known about signaling in Toxoplasma infection, it is likely that protein kinases play a key role in parasite proliferation, differentiation, and probably invasion. To identify optimized new kinase inhibitors for drug development against T. gondii, we screened a library of kinase inhibitor compounds for anti-Toxoplasma activity and host cell cytotoxicity. Pyrimethamine served as a positive control and 0.5% DMSO was used as a negative control. Among the 80 compounds screened, 6 compounds demonstrated ≥ 80% parasite growth inhibition at concentrations at which 5 compounds did not suppress host cell viability, while 3 kinase inhibitors (Bay 11-7082, Tyrphostin AG 1295 and PD-98059) had suppressive effects individually on parasite growth and host cell invasion, but did not strongly induce bradyzoite formation.
巻・号 119(5)
ページ 1675-1681
公開日 2020-5-1
DOI 10.1007/s00436-020-06673-9
PII 10.1007/s00436-020-06673-9
PMID 32236711
PMC PMC7223663
MeSH Animals Antiprotozoal Agents / pharmacology* Cell Differentiation / drug effects Cell Survival / drug effects Flavonoids / pharmacology Humans Nitriles / pharmacology Protein Kinase Inhibitors / pharmacology* Protein Kinases / drug effects* Pyrimethamine / pharmacology Signal Transduction / drug effects Sulfones / pharmacology Toxoplasma / drug effects Toxoplasma / growth & development* Toxoplasma / pathogenicity Toxoplasmosis / drug therapy* Toxoplasmosis / pathology Tyrphostins / pharmacology
IF 1.641
リソース情報
ヒト・動物細胞 Vero(RCB0001)