<i>Plasmodium falciparum</i>: Multidrug resistance

Rout, Subhashree; Mahapatra, Rajani Kanta

doi:10.1111/cbdd.13484

Cited by 44 publications

(31 citation statements)

References 98 publications

(484 reference statements)

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“…Malaria remains an important global health concern as effective vaccines are unavailable and acquired resistance to approved drugs may undermine progress made in the last two decades [1]. As much of the recent progress is attributed to mosquito control [2], increasing rates of insecticide resistance in these disease vectors is also worrisome for achieving the goal of malaria eradication [3].…”

Section: Introductionmentioning

confidence: 99%

Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross

et al. 2020

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Malaria parasites activate a broad-selectivity ion channel on their host erythrocyte membrane to obtain essential nutrients from the bloodstream. This conserved channel, known as the plasmodial surface anion channel (PSAC), has been linked to parasite clag3 genes in P. falciparum, but epigenetic switching between the two copies of this gene hinders clear understanding of how the encoded protein determines PSAC activity. Here, we used linkage analysis in a P. falciparum cross where one parent carries a single clag3 gene to overcome the effects of switching and confirm a primary role of the clag3 product with high confidence. Despite Mendelian inheritance, CLAG3 conditional knockdown revealed remarkably preserved nutrient and solute uptake. Even more surprisingly, transport remained sensitive to a CLAG3 isoform-specific inhibitor despite quantitative knockdown, indicating that low doses of the CLAG3 transgene are sufficient to confer block. We then produced a complete CLAG3 knockout line and found it exhibits an incomplete loss of transport activity, in contrast to rhoph2 and rhoph3, two PSAC-associated genes that cannot be disrupted because nutrient uptake is abolished in their absence. Although the CLAG3 knockout did not incur a fitness cost under standard nutrient-rich culture conditions, this parasite could not be propagated in a modified medium that more closely resembles human plasma. These studies implicate oligomerization of CLAG paralogs encoded by various chromosomes in channel formation. They also reveal that CLAG3 is dispensable under standard in vitro conditions but required for propagation under physiological conditions.

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Section: Introductionmentioning

confidence: 99%

Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross

et al. 2020

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“…[ 5,6 ] Despite tremendous progress, the efficacy of ARTs is being increasingly jeopardized by the emergence and spread of P. falciparum strains that are resistant to artemisinin derivatives and to their partner drugs, as evidenced by the fact that no significant progress in reducing global malaria cases was made from 2015 to 2017, endangering the future efficacy of ACTs. [ 7,8 ] Thus, it is urgent to develop new antidotes against malaria, especially drug‐resistant malaria.…”

Section: Introductionmentioning

confidence: 99%

Chalcone hybrids and their antimalarial activity

Cheng

Yang

Huang

et al. 2020

Archiv der Pharmazie

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Malaria, one of the most striking, re‐emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug‐resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.

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“…The increase in global drug resistance in the malaria-endemic areas has significantly reduced the potency of most current used antimalarial compounds. In order to solve this problem, the development of new antimalarial drug candidates with novel potential mechanisms of action is urgently needed [7][8][9][10] . Efforts to discover new 4-aminoquinoline derivatives are ongoing.…”

Section: Introductionmentioning

confidence: 99%