Design and synthesis of potential malaria cysteinyl protease inhibitors

Several synthesis routes leading to the rigid heterocyclic 2-pyridone scaffold were explored. The syntheses of the 2-pyridones involved constructing and investigating derivatives with hydrophilic and hydrophobic moieties, using a methodology that seems to have a wide scope. Intermediates as well as the target pyridones were docked into the falcipain-2 active site and tested against chloroquine­ sensitive and resistant Plasmodium falciparum strains; three 3-cyano-2-pyridones showed promising results. Using this collection of synthesis methodologies, a wide variety of di- and tripeptides based on a substituted 2-pyridone scaffold in the P2 position, have become accessible.

Project Details

Basic Science

May 2015

South Africa