Literature DB >> 21995318

Identification of the Schistosoma mansoni molecular target for the antimalarial drug artemether.

Rosalba Lepore1, Silvia Simeoni, Domenico Raimondo, Antonia Caroli, Anna Tramontano, Allegra Via.   

Abstract

Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca²⁺-ATPase of Schistosoma . We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca²⁺-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity.

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Year:  2011        PMID: 21995318     DOI: 10.1021/ci2001764

Source DB:  PubMed          Journal:  J Chem Inf Model        ISSN: 1549-9596            Impact factor:   4.956


  6 in total

1.  Lack of association of the S769N mutation in Plasmodium falciparum SERCA (PfATP6) with resistance to artemisinins.

Authors:  Long Cui; Zenglei Wang; Hongying Jiang; Daniel Parker; Haiyan Wang; Xin-Zhuan Su; Liwang Cui
Journal:  Antimicrob Agents Chemother       Date:  2012-02-21       Impact factor: 5.191

2.  Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.

Authors:  Dylan R Pillai; Rachel Lau; Krishna Khairnar; Rosalba Lepore; Allegra Via; Henry M Staines; Sanjeev Krishna
Journal:  Malar J       Date:  2012-04-27       Impact factor: 2.979

3.  TiPs: a database of therapeutic targets in pathogens and associated tools.

Authors:  Rosalba Lepore; Anna Tramontano; Allegra Via
Journal:  Bioinformatics       Date:  2013-05-21       Impact factor: 6.937

4.  In silico repositioning of approved drugs against Schistosoma mansoni energy metabolism targets.

Authors:  Nicole Melo Calixto; Daniela Braz Dos Santos; José Clecildo Barreto Bezerra; Lourival de Almeida Silva
Journal:  PLoS One       Date:  2018-12-31       Impact factor: 3.240

5.  3-oxoacyl-ACP reductase from Schistosoma japonicum: integrated in silico-in vitro strategy for discovering antischistosomal lead compounds.

Authors:  Jian Liu; Dave Dyer; Jipeng Wang; Shuqi Wang; Xiaofeng Du; Bin Xu; Haobing Zhang; Xiaoning Wang; Wei Hu
Journal:  PLoS One       Date:  2013-06-07       Impact factor: 3.240

Review 6.  Revisiting glucose uptake and metabolism in schistosomes: new molecular insights for improved schistosomiasis therapies.

Authors:  Hong You; Rachel J Stephenson; Geoffrey N Gobert; Donald P McManus
Journal:  Front Genet       Date:  2014-06-11       Impact factor: 4.599

  6 in total

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