Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)

Bradford Hirth, Robert H. Barker, Cassandra A. Celatka, Jeffrey D. Klinger, Hanlan Liu, Bakela Nare, Amarjit Nijjar, Margaret A. Phillips, Edmund Sybertz, Erin K. Willert, Yibin Xiang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Modification of the structure of trypanosomal AdoMetDC inhibitor 1 (MDL73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. Compound 7a exhibits improved potencies against both the trypanosomal AdoMetDC enzyme and parasites, and better blood brain barrier penetration than 1.

Original languageEnglish (US)
Pages (from-to)2916-2919
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number11
DOIs
StatePublished - Jun 1 2009

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Keywords

  • Blood brain barrier
  • Inhibitor
  • Purine
  • S-Adenosylmethionine decarboxylase (AdoMetDC)
  • Sleeping sickness
  • Trypanosomiasis

ASJC Scopus subject areas

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

Cite this

Hirth, B., Barker, R. H., Celatka, C. A., Klinger, J. D., Liu, H., Nare, B., Nijjar, A., Phillips, M. A., Sybertz, E., Willert, E. K., & Xiang, Y. (2009). Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT). Bioorganic and Medicinal Chemistry Letters, 19(11), 2916-2919. https://doi.org/10.1016/j.bmcl.2009.04.096