Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

Jeremy P. Mallari, Anang Shelat, Aaron Kosinski, Conor R. Caffrey, Michele Connelly, Fangyi Zhu, James H. McKerrow, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.

Original languageEnglish
Pages (from-to)2883-2885
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number9
DOIs
StatePublished - May 1 2008

Bibliographical note

Funding Information:
This work was supported by the American Lebanese Syrian Associated Charities (ALSAC) and St. Jude Children’s Research Hospital, NIH Grant AI35707, and the Sandler Family Supporting Foundation.

Keywords

  • African trypanosomiasis
  • Cathepsins
  • HAT
  • Protease inhibitors
  • Rhodesain
  • Sleeping sickness
  • TbCatB
  • Thiosemicarbazone

ASJC Scopus subject areas

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

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