Synergy of ferrous ion on 5-aminolevulinic acid-mediated growth inhibition of Plasmodium falciparum

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Abstract

Heme biosynthesis appeared to be a target of malaria therapy because 5-aminolevulinic acid (ALA), a heme biosynthesis starting material, with light exposure or a high amount of ALA alone reduced Plasmodium falciparum growth to undetectable level. However, the administration of a high dose of ALA is unrealistic for clinical therapy. We found that Fe2+ enhanced P. falciparum-killing potency of ALA and significantly inhibited the parasite growth. The intermediates of heme biosynthesis localized to the parasite organelles, and coproporphyrin III was the most accumulated intermediate. These novel findings may lead to development of a new antimalarial drug using ALA and Fe2+.