2006
DOI: 10.1186/1475-2875-5-112
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Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia

Abstract: Background: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone ® ) and inhibits the cytochrome bc 1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance.

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Cited by 12 publications
(5 citation statements)
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“…Although the mechanism of action of atovaquone, which is in the antiprotozoal hydroxy naphthoquinone group, has not been fully determined, it has been stated that the parasite inhibits mitochondrial electron transport and causes collapse of the mitochondrial membrane by acting on the cytochrome b gene on the mitochondrial inner membrane. 25,26 It is thought that buparvaquone used in the treatment disrupts the mitochondria of the parasite in the early period and therefore, due to its structural similarities, buparvaquone acts similarly to atovaquone used in the treatment of Toxoplasma gondii and malaria. 27,28 Buparvaquone has been reported to show 100-fold increased activation against amastigotes (intracellular parasitic form) compared to other hydroxynaphthoquinones.…”
Section: Resultsmentioning
confidence: 99%
“…Although the mechanism of action of atovaquone, which is in the antiprotozoal hydroxy naphthoquinone group, has not been fully determined, it has been stated that the parasite inhibits mitochondrial electron transport and causes collapse of the mitochondrial membrane by acting on the cytochrome b gene on the mitochondrial inner membrane. 25,26 It is thought that buparvaquone used in the treatment disrupts the mitochondria of the parasite in the early period and therefore, due to its structural similarities, buparvaquone acts similarly to atovaquone used in the treatment of Toxoplasma gondii and malaria. 27,28 Buparvaquone has been reported to show 100-fold increased activation against amastigotes (intracellular parasitic form) compared to other hydroxynaphthoquinones.…”
Section: Resultsmentioning
confidence: 99%
“…Buparvaquone causes the lysis of lymphocytes and erythrocytes invaded by Theileria schizonts and Babesia pyroplasma forms. Although its mechanism of action has not been fully elucidated, it is thought that the drug prevents the mitochondrial electron transport of the protozoon and the pyrimidine synthesis (Sherman, 1998;Gebru et al, 2006) which is necessary for the development and reproduction of protozoa (Hacilarlioglu, 2013). Buparvaquone is thought to have similar effects with atovaquone, which is used in the treatment of malaria and Toxoplasma gondii infection (Mehlhorn 2008).…”
Section: Discussionmentioning
confidence: 99%
“…Some have been associated with mutations in the cytb gene, since in vitro resistance to AP was correlated especially with mutations at codon 268 of that gene [ 39 - 41 ]. A molecular survey from Ethiopia and Gabon detected no mutations in the pfcytb gene of samples from Ethiopia but several different mutations in 10% of Gabonian samples, although AP was not in use in both regions [ 42 ]. Spontaneous mutations are rare but seem to occure independent from drug pressure.…”
Section: Discussionmentioning
confidence: 99%