title: The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species.
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.
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Thais G
authors.initials: TG
authors.lastname: Passalacqua
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Fábio A E
authors.initials: FA
authors.lastname: Torres
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Camila T
authors.initials: CT
authors.lastname: Nogueira
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: de Almeida
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Mayara L
authors.initials: ML
authors.lastname: Del Cistia
authors.affiliation: 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.
authors.forename: Mariana B
authors.initials: MB
authors.lastname: dos Santos
authors.forename: Luis A
authors.initials: LA
authors.lastname: Dutra
authors.forename: Vanderlan da Silva
authors.initials: VS
authors.lastname: Bolzani
authors.affiliation: 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.
authors.forename: Luis O
authors.initials: LO
authors.lastname: Regasini
authors.affiliation: UNESP-School of Pharmaceutical Sciences, Department of Clinical Analyses, Rodovia Araraquara-Jaú, Km 01, Araraquara, SP 14801-902, Brazil.
authors.forename: Márcia A S
authors.initials: MA
authors.lastname: Graminha
authors.affiliation: UNESP-Institute of Chemistry, Department of Biochemistry and Chemical Technology, Rua Professor Francisco Degni, 55, Caixa Postal 355, Araraquara, SP 14800-060, Brazil.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Marchetto
authors.affiliation: 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.
authors.forename: Aderson
authors.initials: A
authors.lastname: Zottis
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology*; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D062105:Molecular Docking Simulation
chemical_list: D000981:Antiprotozoal Agents; D047188:Chalcones; C059354:2',4'-dihydroxychalcone; D005993:Glycerolphosphate Dehydrogenase
keywords: 2′4′-Dihydroxychalcone; Cytotoxicity assay; Docking; Glycerol-3-phosphate dehydrogenase; Leishmania amazonensis; Molecular dynamics