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

Author(s)

Passalacqua, Thais G. ; Torres, Fabio A. E. ; Nogueira, Camila T. ; de Almeida, Leticia ; Del Cistia, Mayara L. ; dos Santos, Mariana B. ; Regasini, Luis O. ; Graminha, Marcia A. S. ; Marchetto, Reinaldo ; Zottis, Aderson

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry Letters; v. 25, n. 17, p. 5-pg., 2015-09-01.

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. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/00360-4 - Antibacterial and Antitumor Drug Design: Applying Advanced Computational Methods for the Identification of New Inhibitor Classes Against Bacterial and Human Topoisomerase Enzyme
• Grantee: Aderson Zottis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral