A new chemotype with promise against Trypanosoma cruzi

Xiaofang Wang, Monica Cal, Marcel Kaiser, Frederick S. Buckner, Galina I. Lepesheva, Austin G. Sanford, Alexander I. Wallick, Paul H. Davis, Jonathan L. Vennerstrom

Research output: Contribution to journalArticle

Abstract

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

Original languageEnglish (US)
Article number126778
JournalBioorganic and Medicinal Chemistry Letters
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Trypanosoma cruzi
Sulfonamides
Liver Microsomes
Liver
Functional groups
Parasites
benzamide

Keywords

  • Chagas disease
  • SAR
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Wang, X., Cal, M., Kaiser, M., Buckner, F. S., Lepesheva, G. I., Sanford, A. G., ... Vennerstrom, J. L. (2020). A new chemotype with promise against Trypanosoma cruzi. Bioorganic and Medicinal Chemistry Letters, 30(1), [126778]. https://doi.org/10.1016/j.bmcl.2019.126778

A new chemotype with promise against Trypanosoma cruzi. / Wang, Xiaofang; Cal, Monica; Kaiser, Marcel; Buckner, Frederick S.; Lepesheva, Galina I.; Sanford, Austin G.; Wallick, Alexander I.; Davis, Paul H.; Vennerstrom, Jonathan L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 30, No. 1, 126778, 01.01.2020.

Research output: Contribution to journalArticle

Wang, X, Cal, M, Kaiser, M, Buckner, FS, Lepesheva, GI, Sanford, AG, Wallick, AI, Davis, PH & Vennerstrom, JL 2020, 'A new chemotype with promise against Trypanosoma cruzi', Bioorganic and Medicinal Chemistry Letters, vol. 30, no. 1, 126778. https://doi.org/10.1016/j.bmcl.2019.126778
Wang X, Cal M, Kaiser M, Buckner FS, Lepesheva GI, Sanford AG et al. A new chemotype with promise against Trypanosoma cruzi. Bioorganic and Medicinal Chemistry Letters. 2020 Jan 1;30(1). 126778. https://doi.org/10.1016/j.bmcl.2019.126778
Wang, Xiaofang ; Cal, Monica ; Kaiser, Marcel ; Buckner, Frederick S. ; Lepesheva, Galina I. ; Sanford, Austin G. ; Wallick, Alexander I. ; Davis, Paul H. ; Vennerstrom, Jonathan L. / A new chemotype with promise against Trypanosoma cruzi. In: Bioorganic and Medicinal Chemistry Letters. 2020 ; Vol. 30, No. 1.
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