leishmania parasites coloured sem 200x200Leishmania parasites, coloured scanning electron micrograph. Credit: visualphotos.com

Our work on Leishmania is focused on two main areas—identification of new therapeutic targets and screening of compound libraries. Research efforts focused on the role of the protease subtilisin showed that knockout of subtilisin slows down parasite growth and impacts the trypanothione pathway. These data are compelling from a drug discovery standpoint, as there is already a validated drug target in this pathway, and indicates further exploration of pathway members as drug targets is warranted. Our work has also demonstrated essentiality of CYP51 in Leishmania donovani validating sterol 14-demethylation as therapeutic target for visceral leishmaniasis.

Screening efforts at the CDIPD were initiated in July 2009 with the objective of developing a high throughput assay format capable of screening the activity of small molecules against the intracellular amastigote form of Leishmania parasites. This assay, now developed, is enabling efficient screening of chemical libraries with the most relevant form of the parasite with respect to human disease. We are now identifying leads both for drug development and as tools for further biological exploration of the parasite. With this assay we expect to broaden our collaborations with industrial partners to have access to a large diversity of small molecules and to share an assay more relevant and more adapted to the discovery of active compounds against an intracellular parasite.

pipeline 720x38
  • Novel protease target
  • CYP51 target
  • Bioactive compounds
  • Boron compounds - Anacor
    

 

Leishmaniasis Publications