Journalartikel

Jahr der Veröffentlichung: 1990

Seiten: 59-65

Zeitschrift: Biochemical Pharmacology

Bandnummer: 39

Heftnummer: 1

ISSN: 0006-2952

DOI Link: https://doi.org/10.1016/0006-2952(90)90648-5

Verlag: Elsevier

Abstract: 

10-(4′-Chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (Cowden et al., J Med Chem31:
799, 1988). This flavin analog and two of its derivatives were found to
inhibit the antioxidant flavoenzyme glutathione reductase from human
erythrocytes in its isolated form as well as in hemolysates. The
mixed-type inhibition was completely reversible, the K_i-values
being of the order of 1 μM. Surprisingly, the drugs were not
competitive with FAD, but with GSSG, one of the enzyme's substrates.
Malaria parasite glutathione reductase, extracted from Plasmodium falciparum, could also be inhibited by the compounds. Studies on the effects of the substances on P. falciparum in vitro,
which were demonstrated morphologically and by growth inhibition,
confirmed previous observations with 10-(4′-chlorophenyl)-3-methylflavin
and showed similar parasiticidal characteristics for the two new
derivatives. The activities of five other erythrocytic enzymes tested
were not impaired by the drugs, nor was the nucleotide metabolism of
erythrocytes and/or parasites significantly changed. Permeation into red
blood cells was demonstrated for one compound by ¹⁹F-NMR-spectroscopy.
Inhibition of glutathione reductase might contribute to, or account
for, the antimalarial activity of this group of flavin analogs.

Harvard-Zitierstil: Becker, K., Christopherson, R., Cowden, W., Hunt, H. and Schirmer, R. (1990) Flavin analogs with antimalarial activity as glutathione reductase inhibitors, Biochemical Pharmacology, 39(1), pp. 59-65. https://doi.org/10.1016/0006-2952(90)90648-5

APA-Zitierstil: Becker, K., Christopherson, R., Cowden, W., Hunt, H., & Schirmer, R. (1990). Flavin analogs with antimalarial activity as glutathione reductase inhibitors. Biochemical Pharmacology. 39(1), 59-65. https://doi.org/10.1016/0006-2952(90)90648-5