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

16 Citations (Scopus)

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

Fingerprint

Adenosylmethionine Decarboxylase
African Trypanosomiasis
Blood-Brain Barrier
Parasites
Enzymes

Keywords

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

ASJC Scopus subject areas

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

Cite this

Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT). / Hirth, Bradford; Barker, Robert H.; Celatka, Cassandra A.; Klinger, Jeffrey D.; Liu, Hanlan; Nare, Bakela; Nijjar, Amarjit; Phillips, Margaret A.; Sybertz, Edmund; Willert, Erin K.; Xiang, Yibin.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 11, 01.06.2009, p. 2916-2919.

Research output: Contribution to journalArticle

Hirth, B, Barker, RH, Celatka, CA, Klinger, JD, Liu, H, Nare, B, Nijjar, A, Phillips, MA, Sybertz, E, Willert, EK & Xiang, Y 2009, 'Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 11, pp. 2916-2919. https://doi.org/10.1016/j.bmcl.2009.04.096
Hirth, Bradford ; Barker, Robert H. ; Celatka, Cassandra A. ; Klinger, Jeffrey D. ; Liu, Hanlan ; Nare, Bakela ; Nijjar, Amarjit ; Phillips, Margaret A. ; Sybertz, Edmund ; Willert, Erin K. ; Xiang, Yibin. / Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT). In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 11. pp. 2916-2919.
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