Iron-chelating agents for treating malaria

A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine

“…SNF1 and SNF4 were identified as determinants of resistance in this study, and it is possible that the Snf1p/Snf4p kinase complex plays a cross-talk role in quinine tolerance in yeast by controlling iron homeostasis and glucose de-repression. The importance of iron uptake and metabolism in the response to quinoline antimalarial drugs is highly relevant in a P. falciparum context (Kirk and Saliba 2007), where interference with iron supply has been proposed as a mode of quinoline antimalarial action (Meunier and Robert 2010;Smith and Meremikwu 2003;Solomon et al 2006;Weinberg and Moon 2009). Our results seem to substantiate those of Emerson and co-workers, but the involvement of iron uptake and iron metabolism in the yeast response to quinine might not be a specific one.…”

A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine

“…SNF1 and SNF4 were identified as determinants of resistance in this study, and it is possible that the Snf1p/Snf4p kinase complex plays a cross-talk role in quinine tolerance in yeast by controlling iron homeostasis and glucose de-repression. The importance of iron uptake and metabolism in the response to quinoline antimalarial drugs is highly relevant in a P. falciparum context (Kirk and Saliba 2007), where interference with iron supply has been proposed as a mode of quinoline antimalarial action (Meunier and Robert 2010;Smith and Meremikwu 2003;Solomon et al 2006;Weinberg and Moon 2009). Our results seem to substantiate those of Emerson and co-workers, but the involvement of iron uptake and iron metabolism in the yeast response to quinine might not be a specific one.…”

Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection

“…We tested whether dietary supplementation with a metal chelator might render the ws phenotype more resistant to P. berghei infection and found that it did (Fig 4C). These results are in line with the simple interpretation that, as shown for its stages of development in the mammalian host [62][63][64][65][66][67][68][69][70][71][72][73], Plasmodium also requires access to iron and copper in the mosquito.…”

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

“…Those who received iron and folic acid with or without zinc were 12% (95% CI 2–23, p = 0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1–23%, p = 0.03) more likely to be admitted to hospital [33]. On the other hand, in Zambia, deferoxamine 100 mg/kg/day infused for a total of 72 hours or placebo as adjunct therapy for cerebral malaria, was associated with a trend to increased mortality in the deferoxamine group (32/175, 18.3%) compared to those who received a placebo (19/177, 10.7%), adjusted odds ratio 1.8; 95% CI 0.9–3.6; p  = 0.074 but a reduction in seizure recurrences during admission [34]. It should however be noted that both studies were conducted in areas with high prevalence of iron deficiency and high malaria transmission.…”

A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine

“…SNF1 and SNF4 were identified as determinants of resistance in this study, and it is possible that the Snf1p/Snf4p kinase complex plays a cross-talk role in quinine tolerance in yeast by controlling iron homeostasis and glucose de-repression. The importance of iron uptake and metabolism in the response to quinoline antimalarial drugs is highly relevant in a P. falciparum context (Kirk and Saliba 2007), where interference with iron supply has been proposed as a mode of quinoline antimalarial action (Meunier and Robert 2010;Smith and Meremikwu 2003;Solomon et al 2006;Weinberg and Moon 2009). Our results seem to substantiate those of Emerson and co-workers, but the involvement of iron uptake and iron metabolism in the yeast response to quinine might not be a specific one.…”

Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection

“…We tested whether dietary supplementation with a metal chelator might render the ws phenotype more resistant to P. berghei infection and found that it did (Fig 4C). These results are in line with the simple interpretation that, as shown for its stages of development in the mammalian host [62][63][64][65][66][67][68][69][70][71][72][73], Plasmodium also requires access to iron and copper in the mosquito.…”

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

“…Those who received iron and folic acid with or without zinc were 12% (95% CI 2–23, p = 0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1–23%, p = 0.03) more likely to be admitted to hospital [33]. On the other hand, in Zambia, deferoxamine 100 mg/kg/day infused for a total of 72 hours or placebo as adjunct therapy for cerebral malaria, was associated with a trend to increased mortality in the deferoxamine group (32/175, 18.3%) compared to those who received a placebo (19/177, 10.7%), adjusted odds ratio 1.8; 95% CI 0.9–3.6; p  = 0.074 but a reduction in seizure recurrences during admission [34]. It should however be noted that both studies were conducted in areas with high prevalence of iron deficiency and high malaria transmission.…”

A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine

“…SNF1 and SNF4 were identified as determinants of resistance in this study, and it is possible that the Snf1p/Snf4p kinase complex plays a cross-talk role in quinine tolerance in yeast by controlling iron homeostasis and glucose de-repression. The importance of iron uptake and metabolism in the response to quinoline antimalarial drugs is highly relevant in a P. falciparum context (Kirk and Saliba 2007), where interference with iron supply has been proposed as a mode of quinoline antimalarial action (Meunier and Robert 2010;Smith and Meremikwu 2003;Solomon et al 2006;Weinberg and Moon 2009). Our results seem to substantiate those of Emerson and co-workers, but the involvement of iron uptake and iron metabolism in the yeast response to quinine might not be a specific one.…”

Mosquito metallomics reveal copper and iron as critical factors for Plasmodium infection

“…We tested whether dietary supplementation with a metal chelator might render the ws phenotype more resistant to P. berghei infection and found that it did (Fig 4C). These results are in line with the simple interpretation that, as shown for its stages of development in the mammalian host [62][63][64][65][66][67][68][69][70][71][72][73], Plasmodium also requires access to iron and copper in the mosquito.…”

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

“…Those who received iron and folic acid with or without zinc were 12% (95% CI 2–23, p = 0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1–23%, p = 0.03) more likely to be admitted to hospital [33]. On the other hand, in Zambia, deferoxamine 100 mg/kg/day infused for a total of 72 hours or placebo as adjunct therapy for cerebral malaria, was associated with a trend to increased mortality in the deferoxamine group (32/175, 18.3%) compared to those who received a placebo (19/177, 10.7%), adjusted odds ratio 1.8; 95% CI 0.9–3.6; p  = 0.074 but a reduction in seizure recurrences during admission [34]. It should however be noted that both studies were conducted in areas with high prevalence of iron deficiency and high malaria transmission.…”