Next Article in Journal
Calli Essential Oils Synergize with Lawsone against Multidrug Resistant Pathogens
Next Article in Special Issue
PTEN Inhibition in Human Disease Therapy
Previous Article in Journal
A Chemical Genetics Strategy That Identifies Small Molecules Which Induce the Triple Response in Arabidopsis
Previous Article in Special Issue
Vanadium Compounds as PTP Inhibitors
Open AccessArticle

Novel Mixed-Type Inhibitors of Protein Tyrosine Phosphatase 1B. Kinetic and Computational Studies

1
Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitúa S/N, Durango, Durango C.P. 34000, Mexico
2
Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad de México C.P. 04510, Mexico
3
Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 S/N Fracc. Filadelfia, Gómez Palacio, Durango C.P. 35010, Mexico
4
Instituto de Investigación Científica, Universidad Juárez del Estado de Durango, Av. Universidad S/N, Durango, Durango C.P. 34000, Mexico
*
Author to whom correspondence should be addressed.
Molecules 2017, 22(12), 2262; https://doi.org/10.3390/molecules22122262
Received: 21 November 2017 / Revised: 13 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
The Atlas of Diabetes reports 415 million diabetics in the world, a number that has surpassed in half the expected time the twenty year projection. Type 2 diabetes is the most frequent form of the disease; it is characterized by a defect in the secretion of insulin and a resistance in its target organs. In the search for new antidiabetic drugs, one of the principal strategies consists in promoting the action of insulin. In this sense, attention has been centered in the protein tyrosine phosphatase 1B (PTP1B), a protein whose overexpression or increase of its activity has been related in many studies with insulin resistance. In the present work, a chemical library of 250 compounds was evaluated to determine their inhibition capability on the protein PTP1B. Ten molecules inhibited over the 50% of the activity of the PTP1B, the three most potent molecules were selected for its characterization, reporting Ki values of 5.2, 4.2 and 41.3 µM, for compounds 1, 2, and 3, respectively. Docking and molecular dynamics studies revealed that the three inhibitors made interactions with residues at the secondary binding site to phosphate, exclusive for PTP1B. The data reported here support these compounds as hits for the design more potent and selective inhibitors against PTP1B in the search of new antidiabetic treatment. View Full-Text
Keywords: protein tyrosine phosphatase 1B; type 2 diabetes; benzimidazole derivatives; enzyme inhibition; docking; molecular dynamics protein tyrosine phosphatase 1B; type 2 diabetes; benzimidazole derivatives; enzyme inhibition; docking; molecular dynamics
Show Figures

Figure 1

MDPI and ACS Style

Sarabia-Sánchez, M.J.; Trejo-Soto, P.J.; Velázquez-López, J.M.; Carvente-García, C.; Castillo, R.; Hernández-Campos, A.; Avitia-Domínguez, C.; Enríquez-Mendiola, D.; Sierra-Campos, E.; Valdez-Solana, M.; Salas-Pacheco, J.M.; Téllez-Valencia, A. Novel Mixed-Type Inhibitors of Protein Tyrosine Phosphatase 1B. Kinetic and Computational Studies. Molecules 2017, 22, 2262.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop