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  3. The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species

  • Bioorg Med Chem Lett. 2015 Sep 1;25(17):3564-8. doi: 10.1016/j.bmcl.2015.06.085.
Thais G Passalacqua 1,  Fábio A E Torres 1,  Camila T Nogueira 1,  Leticia de Almeida 1,  Mayara L Del Cistia 1,  Mariana B dos Santos 2,  Luis A Dutra,  Vanderlan da Silva Bolzani,  Luis O Regasini 2,  Márcia A S Graminha 1,  Reinaldo Marchetto 3,  Aderson Zottis 4
Affiliations

Affiliations

  • 1 UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
  • 2 UNESP-Institute of Biosciences, Letters and Exact Sciences, Department of Chemistry and Environmental Sciences, Rua Cristóvão Colombo, 2265, Jardim Nazareth, São José do Rio Preto, SP 15054-000, Brazil.
  • 3 UNESP-Institute of Chemistry, Department of Biochemistry and Chemical Technology, Rua Professor Francisco Degni, 55, Caixa Postal 355, Araraquara, SP 14800-060, Brazil.
  • 4 UNESP-Institute of Chemistry, Department of Biochemistry and Chemical Technology, Rua Professor Francisco Degni, 55, Caixa Postal 355, Araraquara, SP 14800-060, Brazil. Electronic address: zottisad@gmail.com.
PMID: 26169126 DOI: 10.1016/j.bmcl.2015.06.085
Abstract

The Enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of Chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity.

Keywords

2′4′-Dihydroxychalcone; Cytotoxicity assay; Docking; Glycerol-3-phosphate dehydrogenase; Leishmania amazonensis; Molecular dynamics.

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