Microtubule target for new antileishmanial drugs based on ethyl 3-haloacetamidobenzoates

Abdala Hiam, David Sebastien, Bekesi George, Fellous Arlette, Jorge Kalil, Patrice Le Pape*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A new family of antimicrotubule drugs named (3-haloacetamidobenzoyl) ureas and ethyl 3-haloacetamidobenzoates were found to be cytotoxic to the Leishmania parasite protozoa. While the benzoylureas were shown to strongly inhibit in vitro mammalian brain microtubule assembly, the ethyl ester derivatives were characterized as very poor inhibitors of this process. Ethyl 3-chloroacetamidobenzoate, MF29, was found to be the most efficient drug on the promastigote stage of three Leishmania species (IC50: 0.3-1.8 μM). MF29 maintained its activity against the clinical relevant intracellular stage of L. mexicana with IC50 value of 0.33 μM. It was the only compound that exhibits a high activity on all the Leishmania species tested. This compound appeared to alter parasite microtubule organisation as demonstrated by using antibodies directed against microtubule components and more precisely the class of microtubule decorated by the MAP2-like protein. It is interesting to notice that this MAP2-like protein was identified for the first time in a Leishmania parasite.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume21
Issue number3
DOIs
StatePublished - Aug 1 2006

Keywords

  • Antileishmanials
  • Benzoylureas
  • Cytotoxicity
  • Ethyl 3-haloacetamidobenzoates
  • Leishmania
  • Microtubule

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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