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Stephen C. Pelly

Title:
Senior Lecturer
Office: 1037 De Beers Building
Phone: +27 (0)21 808-2180
Fax: +27 (0)21 808-3360
E-mail scpelly@sun.ac.za

Educational Background:
PhD, University of the Witwatersrand

Research Emphasis:
Drug Design, Medicinal Chemistry, Organic Synthesis, Molecular Modelling

 



analitical chemistry
Analytical Chemistry



chemical chemistry Chemical Biology



inorganic chemistry Inorganic Chemistry


organic chemistry Organic Chemistry


physical chemistry Physical Chemistry



polymer science Polymer Science



supramolecular chemistry & materialsSupra- molecular Chemistry
& Materials
 
 
 

Research Summary:
As a medicinal chemistry research group, we combine synthetic organic chemistry and molecular modelling in a rational drug design approach. Currently, most of our research efforts are directed towards developing novel anti-HIV compounds, specifically non-nucleoside reverse transcriptase inhibitors (NNRTIs). In addition, we are working toward novel anti-malarial compounds by targeting key malarial enzymes in the polyamine biosynthetic pathway.

Research Description:

The field of medicinal chemistry is a particularly rewarding
research area as it requires expertise from several diverse
backgrounds for a successful research project. Our main research focus is developing anti-HIV compounds, with a specific interest in designing and synthesizing non-nucleoside reverse transcriptase inhibitors. To this end we incorporate a significant amount of molecular modelling in the design phases of the project in order to identify novel promising compounds which are synthesized to establish proof of concept. Once this has been accomplished, we embark upon a more extensive synthetic campaign to accumulate SAR data which in turn provides valuable guidance for the ongoing modelling phase of the project, thus leading to optimized compounds in an iterative rational design process. This research is particularly relevant in a South African context, given the enormous social and economic problems we face as a result of a particularly high prevalence of the disease in our country, and indeed, sub-Saharan Africa in general.

We are also interested in the similar design and synthesis of novel anti-malarial compounds, specifically targeting the enzyme Spermidine Synthase. Malaria is another disease which places an economic burden on developing nations and therefore it is of the utmost importance that nations who are afflicted by the disease are proactive in seeking new anti-malarial drug molecules.

This research is made possible by well-equipped laboratories with access to all the required spectroscopic services (in particular, NMR, mass spectrometry and single crystal X-ray diffractometry) as well as modern molecular modeling facilities. Collaborations with groups (both national and international) provides the expertise in areas such as whole cell and enzymatic assays, which are so critical to the overall success of the projects.

 
 
     

Selected Publications:

  • Novel cyclopropyl-indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors. M. Hassam, A. E. Basson, D. C. Liotta, L. Morris, W. A. L. van Otterlo and S. C. Pelly. ACS Medicinal Chemistry Letters, 2012, 3, 470-475.
  • In search of a treatment for HIV – current therapies and the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs). C. Reynolds, C. B. de Koning, S. C. Pelly, W. A. L. van Otterlo and M. L. Bode. Chemical Society Reviews, 2012, 41, 4657-4670.
  • Bulbispermine: a crinine-type Amaryllidaceae alkaloid exhibiting cytostatic activity toward apoptosis-resistant glioma cells. G. Luchetti, R. Johnston, V. Mathieu, F. Lefranc, K. Hayden, A. Andolfi, D. Lamoral-Theys, M. R. Reisenauer, C. Champion, S. C.  Pelly, W. A. L. van Otterlo, I. Magedov, R. Kiss, A. Evidente, S. Rogelj and A. Kornienko. ChemMedChem, 2012, 7, 815-822.
  • The Antibiotic CJ-15,801 is an antimetabolite that hijacks and then inhibits CoA biosynthesis. R. van der Westhuyzen, J. C. Hammons, J. L. Meier, S. Dahesh, W. J. Moolman, S. C. Pelly, V. Nizet, M. D. Burkart and E. Strauss. Chemistry and Biology, 2012, 19, 559-571.
  • In search of a cytostatic agent derived from the alkaloid lycorine: Synthesis and growth inhibitory properties of lycorine derivatives. N. M. Evdokimov, D. Lamoral-Theys, V. Mathieu, A. Andolfi, L. V. Frolova, S. C. Pelly, W. A van Otterlo, I. V. Magedov, R. Kiss, A. Evidente and A. Kornienko. Bioorganic & Medicinal Chemistry, 2011, 19, 7252-7261.
  • Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors. M. L. Bode, D. Gravestock, S. S. Moleele, C. W. van der Westhuyzen, S. C. Pelly, P. A. Steenkamp, H. C. Hoppe, T. Khan, L. A. Nkabinde, Bioorganic & Medicinal Chemistry 2011, 19, 4227-4237.
  • Arginine 15 stabilizes an SNAr reaction transition state and the binding of anionic ligands at the active site of human glutathione transferase A1-1. S. Gildenhuys, M. Dobreva, N. Kinsley, Y. Sayed, J. Burke, S. Pelly, G. P. Gordon, M. Sayed, T. Sewell, H. W. Dirr, Biophysical Chemistry 2010, 146, 118-125.
  • Stereoselective syntheses of the 2-isopropenyl-2,3-dihydrobenzofuran nucleus: Potential chiral building blocks for the syntheses of tremetone, hydroxytremetone, and rotenone. S. C. Pelly, S. Govender, M. A. Fernandes, H.-G. Schmalz, C. B. de Koning, The Journal of Organic Chemistry 2007, 72, 2857-2864.
  • Metathesis reactions for the synthesis of ring-fused carbazoles. S. C. Pelly, C. J. Parkinson, W. A. L. van Otterlo, C. B. de Koning, The Journal of Organic Chemistry 2005, 70, 10474-10481.
   
 
 
 
 
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