%0 Journal Article
%T Disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics
%A Rodrigues
%A Juan Ricardo
%A Lourenco
%A Diana
%A Gamboa
%A Neira
%J Revista do Instituto de Medicina Tropical de S£¿o Paulo
%D 2011
%I Instituto de Medicina Tropical
%R 10.1590/S0036-46652011000100005
%X plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. during this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or £¿-hematin. in this context, a group of azole antimycotics, clotrimazole (ctz), ketoconazole (ktz) and fluconazole (fcz), were investigated for their abilities to inhibit £¿-hematin synthesis (i£¿hs) and hemoglobin proteolysis (ihbp) in vitro. the £¿-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by sds-page 12.5%, followed by densitometric analysis. compounds were also assayed in vivo in a malaria murine model. ctz and ktz exhibited the maximal effects inhibiting both biochemical events, showing inhibition of ¦Â-hematin synthesis (ic50 values of 12.4 ¡À 0.9 ¦Ìm and 14.4 ¡À 1.4 ¦Ìm respectively) and inhibition of hemoglobin proteolysis (80.1 ¡À 2.0% and 55.3 ¡À 3.6%, respectively). there is a broad correlation to the in vivo results, especially ctz, which reduced the parasitemia (%p) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ¡À 3.0% compared to 26.6 ¡À 3.7%, p = 0.014) and prolonged the survival days post-infection. the results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.
%K £¿-hematin synthesis
%K azole antimycotics
%K hemoglobin degradation
%K plasmodium berghei.
%U http://www.scielo.br/scielo.php?script=sci_abstract&pid=S0036-46652011000100005&lng=en&nrm=iso&tlng=en