Heme Polymerization Inhibitory Activity (HPIA) of N-alkyl and N-benzyl-1,10 Phenanthroline Derivatives as Antimalaria

Malaria parasite metabolizes hemoglobin and detoxifies the resulting toxic ferriprotoporphyrin IX by polymerization into a crystal insoluble pigment, known as hemozoin. A polymer identical to hemozoin, β-hematin, can be obtained in vitro from hematin at acidic pH. Quinoline-containing antimalarials (e.g. chloroquine) inhibit the formation of polymer. Thus, heme polymerization is an essensial and unique pharmacological target of antimalarial drugs. Previous study on in vitro and in vivo antiplasmodial activity showed that N-alkyl and N-benzyl-1,10phenanthroline derivatives viz. (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride and, (1)-N-benzyl-1,10-phenanthrolinium iodide were potential as antiplasmodial. This study was conducted to investigate the posibility mechanism of action of those compounds on a simple in vitro micro assay of heme polymerization. The IC50 HPIA of N-alkyl and N-benzyl-1,10-phenanthroline derivatives were ranging from 35.54 mM to 62.08 mM while the IC50 HPIA of chloroquine was 3.49 mM. Our result showed that N-alkyl and N-benzyl-1,10-phenanthroline derivatives have effect on heme polymerization inhibitory