Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Investigation and Development of Substituted 4-cyano-3-methylisoquinoline Derivatives against Plasmodium falciparum (#169)

Robabeh Kalhor 1 , Paul R Gilson 2 , Belinda M Abbott 1
  1. Department of Biochemistry and Genetics, La Trobe University, Melbourne, VICTORIA, Australia
  2. Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, Victoria, Australia

According to the World Health Organization, 214 million people suffered from malaria in 2015 and some 438,000 of them didn’t survive. Plasmodium falciparum, the most fatal malaria parasite species, causes the most severe form of this disease and is the leading cause of death in Africa. P. falciparum has shown resistance to anti-malarial drugs, diminishing their therapeutic efficacy and presents a major barrier to disease management.

This presentation reports current results from our work which is aimed at the efficient synthesis of novel isoquinolines and study of their potential anti-malarial activities. Initial screening of these small molecules in a parasite cellular assay has been undertaken on asexual blood stage parasites of Plasmodium falciparum 3D7 and chloroquine-resistant W2mef strains using the colorimetric Malstat assay that measures the amount of parasite enzyme lactate dehydrogenase (LDH) and is positively correlated with parasite proliferation. Several compounds have been found to have IC50 values in the sub-micromolar range.