Synthesis and biological evaluation of some pyrazole derivatives as anti-malarial agents.

Novel series of pyrazole derivatives were synthesized and tested for their in vivo anti-malarial activity using mice infected with chloroquine sensitive P. berghei at a dose level of 50 µmol/kg. The most active compounds were further tested in vitro against chloroquine resistant (RKL9) strain of P. falciparum. The in vivo anti-malarial activity study indicated that compounds 2a, 2b, 8a and 8b had mean percent suppression of 85%, 83%, 95% and 97%, respectively at equimolar dose level of the standard drug chloroquine diphosphate. Moreover, compounds 2a, 2b, 8a and 8b showed in vitro IC(50) values lower (p < 0.05) than that of the standard drug chloroquine phosphate (0.188 ± 0.003  µM) using the RKL9 strain. Compound 8b was the most active with IC(50) of 0.033 ± 0.014  µM. Generally, among the tested compounds, those containing a free carboxylic acid functional group on the pyrazole ring were the most active and this finding was supported by the docking results performed for the active compounds. The acute toxicity studies of the active compounds revealed that they have a good safety profile.