Antimalarial action of flavin analogues seems not be due to inhibition of glutathione reductase of host erythrocytes.
A series of 10-(4'-chlorophenyl)-3-substituted flavins (1a-f) were examined with respect to their antimalarial properties. They were tested against Plasmodium falciparum in vitro and Plasmodium vinckei vinckei in vivo. The proposition that they might act through glutathione reductase (GR) (EC 1.6.4.2) inhibition has been studied. Inhibition of P. falciparum in vitro by these compounds shows only slight variation between analogues; in contrast, inhibition of human erythrocyte GR by members of the same series is highly variable, indicating that this is probably not their primary mode of antimalarial action. Results of the P. vinckei vinckei screen showed that 10-(4'-chlorophenyl)-3-methyl,3-ethyl and 3-propyl substituted flavins are active in vivo over the dose range screened (10-70 mg/kg).
Halladay
P K
PK
Division of Cell Biology, John Curtin School of Medical Research, Canberra, A.C.T, Australia.
Hunt
N H
NH
Butcher
G A
GA
Cowden
W B
WB
D000818:Animals; D000962:Antimalarials; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000201:enzymology*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D012256:Riboflavin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000962:Antimalarials; D005980:Glutathione Reductase; D012256:Riboflavin