<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1870-249X</journal-id>
<journal-title><![CDATA[Journal of the Mexican Chemical Society]]></journal-title>
<abbrev-journal-title><![CDATA[J. Mex. Chem. Soc]]></abbrev-journal-title>
<issn>1870-249X</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Química de México A.C.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1870-249X2024000400609</article-id>
<article-id pub-id-type="doi">10.29356/jmcs.v68i4.2284</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Design and Synthesis of Barbiturates and Hydantoins with Multitarget Antidiabetic Effect]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Juárez-Cruz]]></surname>
<given-names><![CDATA[Samantha]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Estrada-Soto]]></surname>
<given-names><![CDATA[Samuel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Colín-Lozano]]></surname>
<given-names><![CDATA[Blanca]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Marquina-Rodríguez]]></surname>
<given-names><![CDATA[Hugo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Delgado-Aguilar]]></surname>
<given-names><![CDATA[Thalía]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Martínez-Conde]]></surname>
<given-names><![CDATA[Carlos]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gutiérrez-Hernández]]></surname>
<given-names><![CDATA[Abraham]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hernández-Núñez]]></surname>
<given-names><![CDATA[Emanuel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Giacoman-Martínez]]></surname>
<given-names><![CDATA[Abraham]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Almanza-Pérez]]></surname>
<given-names><![CDATA[Julio Cesar]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Navarrete-Vazquez]]></surname>
<given-names><![CDATA[Gabriel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad Autónoma del Estado de Morelos Facultad de Farmacia ]]></institution>
<addr-line><![CDATA[Cuernavaca Morelos]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Instituto Politécnico Nacional Departamento de Recursos del Mar Centro de Investigación y de Estudios Avanzados]]></institution>
<addr-line><![CDATA[Mérida Yucatán]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad Autónoma Metropolitana  Depto. Ciencias de la Salud]]></institution>
<addr-line><![CDATA[Iztapalapa México City]]></addr-line>
<country>Mexico</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2024</year>
</pub-date>
<volume>68</volume>
<numero>4</numero>
<fpage>609</fpage>
<lpage>623</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S1870-249X2024000400609&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S1870-249X2024000400609&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S1870-249X2024000400609&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract. In current work, we prepared a series of ten 4-aryloxy-5-benzylidenebarbiturates and hydantoins as 1,3-thiazolidine-2,4-dione bioisosteres. An in silico pharmacological consensus analysis (PHACA) was conducted to assess the pharmacokinetic, pharmacodynamics, biopharmaceutical, and toxicological properties of compounds 1-10. The goal was to identify computationally safe hits using a color-coded system resembling a traffic light. The compounds identified as safe computational hits through PHACA were 1, 2, and 4 from the barbiturate series, which were then selected by in vitro assays targeting PPAR-&#947;, GPR40, and GLUT-4 gene expression. Additionally, these three compounds underwent in vivo evaluation through a glucose tolerance curve assay conducted on normoglycemic mice. Compounds 1 and 4 exhibited antihyperglycemic effects within the first thirty minutes post-administration. Molecular docking studies were conducted to clarify the dual effect and binding mode of compounds 1, 2 and 4 on PPAR-&#947; and GPR40. Compounds 1 and 4 exhibited robust in vitro and in vivo efficacy and could be considered as multitarget modulators with antidiabetic effect.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen. En este trabajo se preparó una serie de diez 4-ariloxi-5-bencilidenobarbituratos e hidantoínas como bioisósteros de la 1,3-tiazolidina-2,4-diona. Se realizó un análisis de consenso farmacológico in silico (PHACA) para evaluar las propiedades farmacocinéticas, farmacodinámicas, biofarmacéuticas y toxicológicas de los compuestos 1-10. El objetivo era identificar hits computacionales seguros utilizando un sistema codificado por colores que se asemeja a un semáforo. Los compuestos identificados como hits computacionales seguros fueron 1, 2 y 4 de la serie de barbituratos, que se eligieron para ensayos in vitro dirigidos a la expresión génica de PPAR-&#947;, GPR40 y GLUT-4. Además, estos tres compuestos se sometieron a una evaluación in vivo mediante un ensayo de curva de tolerancia a la glucosa realizado en ratones normoglucémicos. Los compuestos 1 y 4 exhibieron efectos antihiperglucémicos dentro de los primeros treinta minutos posteriores a la administración. Se realizaron estudios de acoplamiento molecular para clarificar el efecto dual y el modo de unión de los compuestos 1, 2 y 4 en PPAR-&#947; y GPR40. Los compuestos 1 y 4 exhibieron una sólida eficacia in vitro e in vivo, por lo que pueden considerarse moduladores polifarmacológicos con efecto antidiabético.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Diabetes]]></kwd>
<kwd lng="en"><![CDATA[bioisosteres]]></kwd>
<kwd lng="en"><![CDATA[multitarget effect]]></kwd>
<kwd lng="en"><![CDATA[pharmacological consensus analysis]]></kwd>
<kwd lng="es"><![CDATA[Diabetes]]></kwd>
<kwd lng="es"><![CDATA[bioisósteros]]></kwd>
<kwd lng="es"><![CDATA[efecto polifarmacológico]]></kwd>
<kwd lng="es"><![CDATA[análisis de consenso farmacológico]]></kwd>
</kwd-group>
</article-meta>
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