Design, Synthesis and <em>In Combo</em> Antidiabetic Bioevaluation of Multitarget Phenylpropanoic Acids

• DOI: 10.20944/preprints201801.0079.v1
• Publication Date: 2018-01-12T02:36:43Z
• Authors: Blanca Colín-Lozano; Samuel Estrada-Soto; Fabiola Chávez-Silva; Abraham Gutiérrez...; Litzia Cerón-Romero; Abraham Giacoman-...; Julio Cesar Alman...; Emanuel Hernández...; Zhilong Wang; Xin Xie; Mario Cappiello; Francesco Balestri; Umberto Mura; Gabriel Navarrete...
• Keywords: IC50

We synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids using an easy and short step synthetic route. All compounds were tested in vitro against set four protein targets identified as key elements diabetes: GPR40, aldose reductase (AKR1B1), PPAR&amp;gamma; GLUT-4. Compound 1 displayed EC50 value 0.075 &amp;mu;M GPR40 was AKR1B1 inhibitor, showing IC50 = 7.4 &amp;mu;M. Compounds 2 3 behave inhibitors, agonists showed increase to 4-times the mRNA expression PPAR&amp;gamma;, well GLUT-4 levels. Docking studies conducted order explain polypharmacological mode action interaction binding most active on these targets. 1-3 vivo at 100 mg/kg dose, being orally actives, reducing glucose levels non insulin-dependent diabetes mellitus mice model. robust efficacy, could be considered promising multitarget antidiabetic drug candidates. This is first report single molecule with target action.