Author, as appears in the article.: Jose Ojeda-Montes, Maria; Ardid-Ruiz, Andrea; Tomas-Hernandez, Sarah; Gimeno, Aleix; Cereto-Massague, Adria; Beltran-Debon, Raul; Mulero, Miquel; Garcia-Vallve, Santiago; Pujadas, Gerard; Valls, Cristina
Department: Bioquímica i Biotecnologia
URV's Author/s: ARDID RUIZ, ANDREA / Beltrán Debón, Raúl Alejandro / Cereto Massagué, Adrián José / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard / TOMAS HERNÁNDEZ, SARA / Valls Bautista, Cristina
Keywords: Structure-based drug design Structure-activity relationship Stereoisomerism Protein–ligand docking Protein-ligand docking Protein structure, tertiary Protein isoforms Plant extracts Phenylpropanolamine Natural compounds Molecular docking simulation Inhibitory concentration 50 Hypoglycemic agents Ephedrine Ephedra extract Ephedra Drug design Dipeptidyl-peptidase iv inhibitors Dipeptidyl peptidase 4 Binding, competitive Binding sites Alkaloids
Abstract: © 2017 2017 Future Science Ltd. Aim: Extracts from Ephedra species have been reported to be effective as antidiabetics. A previous in silico study predicted that ephedrine and five ephedrine derivatives could contribute to the described antidiabetic effect of Ephedra extracts by inhibiting dipeptidyl peptidase IV (DPP-IV). Finding selective DPP-IV inhibitors is a current therapeutic strategy for Type 2 diabetes mellitus management. Therefore, the main aim of this work is to experimentally determine whether these alkaloids are DPP-IV inhibitors. Materials & methods: The DPP-IV inhibition of Ephedra's alkaloids was determined via a competitive-binding assay. Then, computational analyses were used in order to find out the protein-ligand interactions and to perform a lead optimization. Results: Our results show that all six molecules are DPP-IV inhibitors, with IC50 ranging from 124 μM for ephedrine to 28 mM for N-methylpseudoephedrine. Conclusion: Further computational analysis shows how Ephedra's alkaloids could be used as promising lead molecules for designing more potent and selective DPP-IV inhibitors.
Thematic Areas: Saúde coletiva Química Pharmacology Odontología Molecular medicine Medicina ii General medicine Farmacia Engenharias iv Enfermagem Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciência da computação Chemistry, medicinal Biotecnología Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 17568919
Author's mail: adrianjose.cereto@urv.cat cristina.valls@urv.cat miquel.mulero@urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat raul.beltran@urv.cat
Author identifier: 0000-0001-5583-5695 0000-0002-0348-7497 0000-0003-2598-8089 0000-0001-9691-1906
Record's date: 2024-11-23
Papper version: info:eu-repo/semantics/acceptedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Future Medicinal Chemistry. 9 (18): 2129-2146
APA: Jose Ojeda-Montes, Maria; Ardid-Ruiz, Andrea; Tomas-Hernandez, Sarah; Gimeno, Aleix; Cereto-Massague, Adria; Beltran-Debon, Raul; Mulero, Miquel; Garc (2017). Ephedrine as a lead compound for the development of new DPP-IV inhibitors. Future Medicinal Chemistry, 9(18), 2129-2146. DOI: 10.4155/fmc-2017-0080
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications
Repositori URV