Synergistic interaction between monodesbutyl-benflumetol and retinol in Plasmodium falciparum.
The blood schizontocidal activity of monodesbutyl-benflumetol (DBB), retinol (RET) and combinations (DBB-RET) at retinol concentrations corresponding to the 50th, 65th and 80th percentile of physiological retinol concentrations in healthy adults has been investigated in Plasmodium falciparum. Parallel in vitro tests with DBB, RET and the 3 DBB-RET combinations were carried out with 26 fresh parasite isolates from northwestern Thailand, following the WHO standard protocol Mark II for determining the inhibition of schizont maturation. The EC(50) values for DBB, RET and for DBB in DBB-RET low, medium and high were 5.72 nM, 561.83 nM, 1.68 nM, 0.60 nM and 0.07 nM, respectively, the EC(90) values 44.14 nM, 9338.60 nM, 49.00 nM, 28.48 nM and 8.94 nM. The geometric mean cut-off concentrations of schizont maturation for DBB alone and for DBB in DBB-RET low, medium and high were 153.20 nM, 62.93nM, 34.00 nM and 13.74 nM, respectively, indicating significant synergistic interaction between DBB and retinol. The degree of synergism increases with the retinol concentration in the combination and is highest at the EC(99) level for DBB.
Parizek
Maria
M
Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Sirichaisinthop
Jeeraphat
J
Wernsdorfer
Gunther
G
Noedl
Harald
H
Kollaritsch
Herwig
H
Wernsdorfer
Walther H
WH
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D053626:Atovaquone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage*; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D007928:Lethal Dose 50; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage*
D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D014801:Vitamin A; D000078102:Lumefantrine; D053626:Atovaquone