title: Synthesis, in vitro and in silico studies of a PPARγ and GLUT-4 modulator with hypoglycemic effect.
abstract: Compound {4-[({4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}acetyl)amino]phenoxy}acetic acid (1) was prepared and the in vitro relative expression of PPARγ, GLUT-4 and PPARα, was estimated. Compound 1 showed an increase of 2-fold in the mRNA expression of PPARγ isoform, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus (NIDDM) rat model. The in vivo results indicated a significant decrease of plasma glucose levels, during the 7 h post-administration. Also, we performed a molecular docking of compound 1 into the ligand binding pocket of PPARγ, showing important short contacts with residues Ser289, His323 and His449 in the active site.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico. Electronic address: gabriel_navarrete@uaem.mx.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico; Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, D-48149 Münster, Germany.
authors.forename: Héctor
authors.initials: H
authors.lastname: Torres-Gómez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Hidalgo-Figueroa
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Ramírez-Espinosa
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
authors.affiliation: Mayo Clinic, Scottsdale, AZ 85259, USA.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.affiliation: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
authors.forename: Ismael
authors.initials: I
authors.lastname: León-Rivera
authors.affiliation: Laboratorio de Farmacología, Depto. Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico, D.F. 09340, Mexico.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Alarcón-Aguilar
authors.affiliation: Laboratorio de Farmacología, Depto. Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico, D.F. 09340, Mexico.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Almanza-Pérez
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D008024:Ligands; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C000596734:4-(((4-((Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl)phenoxy)acetyl)amino)phenoxy)acetic acid; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D053778:Thiazolidines
keywords: Diabetes; Molecular docking; PPAR