Provitamin B5 (pantothenol) inhibits growth of the intraerythrocytic malaria parasite.
Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite Plasmodium falciparum. Instead, pantothenol inhibited the in vitro growth of P. falciparum via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase. Oral administration of pantothenol to mice infected with the murine parasite Plasmodium vinckei vinckei resulted in a significant inhibition of parasite proliferation. This study highlights the potential of the coenzyme A biosynthesis pathway in general, and pantothenate kinase in particular, as an antimalarial drug target.
Saliba
Kevin J
KJ
School of Biochemistry and Molecular Biology, Faculty of Science, The Australian National University, Canberra ACT 0200, Australia. kevin.saliba@anu.edu.au
Ferru
Isabelle
I
Kirk
Kiaran
K
D000818:Animals; D000962:Antimalarials; D001693:Biological Transport, Active; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007202:Indicators and Reagents; D019169:Jurkat Cells; D008288:Malaria / Q000188:drug therapy / Q000523:psychology; D051379:Mice; D008807:Mice, Inbred BALB C; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development*
D000962:Antimalarials; D007202:Indicators and Reagents; D010205:Pantothenic Acid; C007288:dexpanthenol