Skip to content

Advertisement

You're viewing the new version of our site. Please leave us feedback.

Learn more

BMC Proceedings

Open Access

Repositioning of new potential schistosomicidal drugs using chemogenomic strategy

  • Arthur Scalzitti Duarte1,
  • José Clecildo Barreto Bezerra1,
  • Lourival de Almeida Silva2,
  • Bruno Junior Neves3,
  • Carolina Andrade3,
  • Marina Clare Vinaud1 and
  • Clélia Christina Mello Silva4
BMC Proceedings20148(Suppl 4):P55

https://doi.org/10.1186/1753-6561-8-S4-P55

Published: 1 October 2014

Background

Schistosomiasis remains a severe problem of public health in developing countries [1]. Several reports show that praziquantel, the drug of choice for treating schistosomiasis, can select Schistosoma mansoni strains resistant to the drug. Thus, developing new drugs against this parasitosis is a highly desirable goal [2]. In this context, enzymes involved in energetic metabolism could represent attractive drug targets for novel anti-schistosome chemotherapies [3, 4]. We report a chemogenomic strategy for identification of approved drugs that may be able to interfere with energetic metabolism of the Schistosoma mansoni.

Methods

The chemogenomic study was performed on a list containing 734 genes involved in oxidative phosphorylation (n = 45); nitrogen metabolism (n = 642); glycolysis (n = 11); citrate cycle (n = 10); and others (n = 26). Next, it was obtained from the GeneDB S. mansoni genome database individual information for genes (amino acid sequence in FASTA format, product name, and biological process). Each of these protein sequences was treated as a potential drug target and used to screen three freely available databases (DrugBank, STITCH 3.1, and TTD) based in the concept of the target sequence similarity. The targets with E-value score ≤ 10-5 and score ≥ 0.7 were considered for further analyses.

Results and conclusions

We were able to identify several drugs that are expected to interact with 6 targets involved in nitrogen metabolism (carbonic anhydrase II and carbonic anidrase), citrate cycle (succinate dehydrogenase), oxidative phosphorylation (ATP synthase delta chain and NADH-ubiquinone oxidoreductase mitochondrial precursor), and glutamate metabolism (glutaminase). One of these targets was associated with thiabendazole, whose activity has been previously evaluated against S. mansoni. [5]. However, 18 drugs were predicted to have activity against other targets and have never been evaluated against schistosoma parasites (e.g., acetazolamide, doxorubicin, morantel tartrate, axantel pamoate, thiabendazole, and menthol). Our next step is to experimentally screen these drugs against S. mansoni. Being a cost and time saving route, drug repositioning is expected to accelerate the discovery of new anti-schistosome chemotherapies.

Financial support: FAPEG/Goiás.

Authors’ Affiliations

(1)
LAERPH, IPTSP, Federal University of Goiás
(2)
Instituto Federal Goiano
(3)
LabMol, FF, Federal University of Goiás
(4)
LEE/IOC, Fiocruz

References

  1. Gryseels B, Polman K, Clerinx J, Kestens L: Human schistosomiasis. Lancet. 2006, 368: 1106-18.View ArticlePubMedGoogle Scholar
  2. Thétiot-Laurent Sa-L, Boissier J, Robert A, Meunier B: Schistosomiasis chemotherapy. Angewandte Chemie (International ed in English). 2013, 52: 7936-56.View ArticleGoogle Scholar
  3. Van Oordt BE, Tielens AG, Van den Bergh SG: The energy metabolism of Schistosoma mansoni during its development in the hamster. Parasitology research. 1988, 75: 31-5.View ArticlePubMedGoogle Scholar
  4. Smith TM, Brown JN: Tricarboxylic acid cycle enzyme activities in adult Schistosoma mansoni and Schistosoma japonicum. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1977, 71: 329-30.View ArticlePubMedGoogle Scholar
  5. Pancera CF, Alves AL, Paschoalotti MA, Chieffi PP: Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice. Revista do Instituto de Medicina Tropical de São Paulo. 2013, 39: 159-63.View ArticleGoogle Scholar

Copyright

© Duarte et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement