NEW POTENTIAL ANTIMALARIAL AGENTS: SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME SCHIFF BASE LIGAND AS ANTIMALARIAL AGENTS

Plasmodium falciparum is the protozoan parasite responsible for the majority of life-threatening cases of human malaria, causing more than one million deaths a year. The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. At present, α-carbonic anhydrase (CA) genes are identified in limited numbers of parasites in both protozoa and helminthes, however, the malarial genes are found in four species of Plasmodium. The CA gene of P. falciparum encodes an α- carbonic anhydrase enzyme possessing catalytic properties distinct of that of the human host CA I and II isozymes. P. falciparum native and recombinant enzymes have been prepared. Eighteen new schiff base ligand (AA01-AA18) related to previously reported potent blood schizontocidal antimalarial agent, 2-tertbutylprimaquine were synthesized and evaluated for in vivo antimalarial activities against drug-sensitive Plasmodium falciparum strain. Acute toxicity studies found that synthesized compounds were less toxic than the parent compound chloroquine, while preserving the desired antimalarial activity. Five of the analogues (AA3, AA6, AA-4, AA-9 and A-10) have exhibited curative antimalarial activity at a dose of 25mg/kg/day×4 and produced suppressive activity at a lower dose of 10 mg/kg/day×4The results of antimalarial activity showed that the ligand AA-1 exhibits moderately active while complex AA-6 exhibits good activity for chloroquine sensitive and resistant