Identifying and validating new drug targets for Neglected Tropical Diseases

CCOMSTECH-NTD NETWORK JOINT LECTURE SERIES By Professor Patrick G. Steel Department of Chemistry and Biophysical Sciences Institute, Durham University, Durham DH1 3LE, UK


The protozoan kinetoplastid parasites Leishmania spp, Trypanosoma brucei and Trypanosoma cruzi are responsible for potentially fatal diseases that affect over 22 million people worldwide, with an estimated 450 million people at risk. Current therapies are expensive and not widely accessible. In addition, drug toxicity and emerging resistance are major concerns and there is a major need for new tractable drug targets. In this presentation I will describe examples of phenotypic and target-based approaches towards the discovery of new leishmanial drug targets and the identification of tractable chemical starting points for future drug discovery programmes. For the former we have used a natural chalcone, with antileishmanial properties, as a starting point to develop and apply probes to identify the molecular target. In the second, target-based, strategy, we have identified the essential kinetoplastid sphingolipid synthase (SLS) as an attractive pharmaceutical target due to the divergence of function compared with the mammalian orthologous. We have developed screening assays to identify potential inhibitors against the Leishmania major enzyme. One assay identified the OTC antihistamine clemastine fumarate as a potential antileishmanial and I will discuss our efforts to validate and exploit this finding.


Patrick Steel undertook his undergraduate and post-graduate training with Prof Jim Thomas at the University of Oxford. Following a NATO-SERC postdoctoral fellowship with Prof Gilbert Stork at Columbia University NY, he joined the staff at Durham University where he is currently a professor of organic chemistry and chemical biology. His group study problems in organic synthesis (iridium and copper catalysed borylation methodologies) and chemical biology with particular interests in neglected tropical diseases (notably leishmaniasis) and plant chemical biology (plant hormonal signalling and herbicide resistance). He is currently the Head of the Organic Chemistry Section at Durham University and was an elected council member of the Royal Society of Chemistry, Chemistry Biology Interface Division 2013-2019.

 The COMSTECH - NTD NETWORK virtual lecture programme, launched this year, shares the expertise from both our Networks, for academics, professional scientists and anyone interested in Neglected Tropical Diseases (NTDs) to gain or enhance their knowledge, skills and academic connections.

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