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Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase.
Kaur, Supreet; Nieto, Nicholas S; McDonald, Peter; Beck, Josh R; Honzatko, Richard B; Roy, Anuradha; Nelson, Scott W.
Afiliación
  • Kaur S; Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, USA.
  • Nieto NS; Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, USA.
  • McDonald P; High Throughput Screening Laboratory, University of Kansas, Lawrence, KS, USA.
  • Beck JR; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.
  • Honzatko RB; Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, USA.
  • Roy A; High Throughput Screening Laboratory, University of Kansas, Lawrence, KS, USA.
  • Nelson SW; Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, USA.
J Enzyme Inhib Med Chem ; 37(1): 1320-1326, 2022 Dec.
Article en En | MEDLINE | ID: mdl-35514163
Malaria is caused by infection with protozoan parasites of the Plasmodium genus, which is part of the phylum Apicomplexa. Most organisms in this phylum contain a relic plastid called the apicoplast. The apicoplast genome is replicated by a single DNA polymerase (apPOL), which is an attractive target for anti-malarial drugs. We screened small-molecule libraries (206,504 compounds) using a fluorescence-based high-throughput DNA polymerase assay. Dose/response analysis and counter-screening identified 186 specific apPOL inhibitors. Toxicity screening against human HepaRG human cells removed 84 compounds and the remaining were subjected to parasite killing assays using chloroquine resistant P. falciparum parasites. Nine compounds were potent inhibitors of parasite growth and may serve as lead compounds in efforts to discover novel malaria drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apicoplastos / Malaria / Antimaláricos Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apicoplastos / Malaria / Antimaláricos Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido