Authors
M Rajab2; S Rossington2; H Matthews1; M Abubaker2; P Panwar2; J Wilkinson2; N Nirmalan2; 1 Imperial College London; 2 University of Salford Discussion
The importance of calcium in the Plasmodium falciparum parasite's life cycle has been widely reported. Studies have shown that calcium levels are higher in infected RBCs than non-infected ones. Studies have also shown that interfering with calcium signalling can lead to degeneration and eventually parasite death. Likewise calmodulin is thought to play a major role in the parasite's life cycle, particularly in the invasion of RBCs. This supports results of a repositioning study carried out at the University of Salford were 700 patent expired drugs were screened against the multidrug resistant K1 P. falciparum strain. The results showed several calcium channel blockers and calmodulin inhibitors to have antimalarial activity.
The work presented here investigates the antimalarial efficacy of a calcium channel blocker and calmodulin inhibitor MR15 and its synthetic derivatives. Results of the in vitro phenotypic screens on the multidrug resistant K1 P. falciparum strain, HepG2 cytotoxicity assay, hERG safety test and stage specificity analysis have been promising and thus support further SAR studies on the lead compounds.
