Background:
Malaria is one of the most vital infectious diseases caused by protozoan
parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of
malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin,
and antifolates, there is an urgent need to identify new targets for chemotherapy.
Objective:
This study screened novel pyrazole derivatives carrying iminium & benzothiazole group
for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain.
Materials & Methods:
Several pyrazole schiff base hybrids with a wide range of substitution have
been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and
evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria
parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated
by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The
pharmacokinetic properties were also studied using ADME prediction.
Results:
Among all compounds, 6bf and 6bd were found to be potential molecules with EC50
1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base
derivatives occupy the PfFP binding sites and they show good interactions with significant values of
binding energies.
Conclusion:
We provide evidence which implicates pyrazole Schiff base hybrids as potential
prototypes for the development of antimalarial agents.
Inside Cover: Docking Studies of Structurally Diverse Antimalarial Drugs Targeting PfATP6: No Correlation between in silico Binding Affinity and in vitro Antimalarial Activity. (ChemMedChem 9/2009)
