Organic Synthesis and Drug Discovery

Hit Identification

This stage involves identification of unexplored chemical space of known drugs, such as Donepezil for Alzheimer’s disease. This is assisted by computational studies to help rationalise the derivatisation of the unexplored chemical spaces. This process utilises protein crystal structures with different inhibitors bound, to identify important binding interactions between the protein and inhibitors. Which is used to further identify interactions that can be altered by changing the current functional groups of the inhibitor. The aim is to identify potential inhibitors with improved potency and/or ADMET properties, as compared to available drugs.

Hit to Lead

Next, synthesis of analogues exploiting unexplored chemical space using typical organic synthetic approaches, are used to form a focused library. Analogues have various altered functional groups, while the backbone is typically left unaltered.

In-silico studies are also utilised to do docking studies on a much larger virtual library. This library is generated using combinatorial techniques utilising a common scaffold using common organic reactions. Compounds are selected from the docking studies, which show potential increase in activity and/or ADMET properties, are then also synthesised.

Biological Evaluation

Finally, all successfully synthesised compounds are submitted for biological screening against their targeted protein. Compounds are also screened to assess their toxicity and ADMET properties.


  • CSIR - Dr J. Panayides and Dr C. van der Westhuyzen
  • Department of Pharmacology at UP - Prof V. Steenkamp, Werner Cordier

Current Students:

Sergio Lovisa (MSc)
Valerie Ramaotsoa (PhD)
C. Johan van der Westhuizen (PhD)
Divan van Greunen (PhD)
Lupiwana Mpheleki (PhD)
Audu Oluwatosin Yemisi (PhD)
Adigun Rasheed Adewale (PhD)
Ramogale Martha Makuwa (MSc)

Contact Details:

Dr Darren L Riley
Tel: +27(0) 12 420 3097
[email protected]
Office: NS1, Room 4-50

Dr Natasha October
Tel: +27(0) 12 420 4905
[email protected]
Office: NS1, Room 4-46

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