<?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>S1870-249X2024000100170</article-id>
<article-id pub-id-type="doi">10.29356/jmcs.v68i1.2103</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[In Vitro and In Silico Studies of Bis-furyl-pyrrolo[3,4-b]pyridin-5-ones on Dengue Virus]]></article-title>
<article-title xml:lang="es"><![CDATA[Estudios in vitro e in silico de bis-furil-pirrolo[3,4-b]piridin-5-onas en el virus del dengue]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Morales-Salazar]]></surname>
<given-names><![CDATA[Ivette]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Garduño-Albino]]></surname>
<given-names><![CDATA[Carlos E.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Montes-Enríquez]]></surname>
<given-names><![CDATA[Flora P.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gutiérrez-Carrillo]]></surname>
<given-names><![CDATA[Atilano]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rojas-Aguirre]]></surname>
<given-names><![CDATA[Yareli]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Estrada-Toledo]]></surname>
<given-names><![CDATA[Nancy Viridiana]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sandoval-Basilio]]></surname>
<given-names><![CDATA[Jorge]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Alcaraz-Estrada]]></surname>
<given-names><![CDATA[Sofía Lizeth]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Díaz-Cervantes]]></surname>
<given-names><![CDATA[Erik]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González-Zamora]]></surname>
<given-names><![CDATA[Eduardo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Islas-Jácome]]></surname>
<given-names><![CDATA[Alejandro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad Autónoma Metropolitana Departamento de Química ]]></institution>
<addr-line><![CDATA[Ciudad de México ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad Nacional Autónoma de México Instituto de Investigaciones en Materiales Departamento de Polímeros]]></institution>
<addr-line><![CDATA[Ciudad de México ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Health Pharma Professional Research S.A. de C.V. Centro de Investigación Clínica Coordinación de Comités de Evaluación en Salud]]></institution>
<addr-line><![CDATA[Ciudad de México ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad Hipócrates Laboratorio de Biología Molecular ]]></institution>
<addr-line><![CDATA[ Guerrero]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Centro Médico Nacional 20 de Noviembre División de Medicina Genómica ]]></institution>
<addr-line><![CDATA[Ciudad de México ]]></addr-line>
<country>Mexico</country>
</aff>
<aff id="Af6">
<institution><![CDATA[,Universidad de Guanajuato Centro Interdisciplinario del Noreste Departamento de Alimentos]]></institution>
<addr-line><![CDATA[ Guanajuato]]></addr-line>
<country>Mexico</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>03</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>03</month>
<year>2024</year>
</pub-date>
<volume>68</volume>
<numero>1</numero>
<fpage>170</fpage>
<lpage>183</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S1870-249X2024000100170&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S1870-249X2024000100170&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S1870-249X2024000100170&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract. A series of six bis-furyl-pyrrolo[3,4-b]pyridin-5-ones synthesized via an Ugi-Zhu reaction coupled to a cascade process [aza Diels-Alder cycloaddition/N-acylation/aromatization] were evaluated in vitro against Dengue virus serotype 4 infection, and the Dengue virus replicon system encoding a Renilla luciferase gen reporter. Also, in silico studies on the non-structural protein 3 (NS3), a flavivirus protease comprising an attractive target for development of therapeutic antivirals bound to non-structural protein 2B (NS3-NS2B) were performed. The in vitro results showed that compounds 1a and 1b reduced the expression of Renilla luciferase in 44.2 and 31.6%, respectively. Additionally, the same compounds decreased viral load, thus revealing their potential activity against Dengue virus serotype 4. From in silico simulations, it was developed a NS3-NS2B model, which was used as a target for the studied molecules. Computational results agree with experimental data, showing that 1a is the best ligand. Finally, a pharmacophoric model was computed for NS3-NS2B, which shows that the ligands need two hydrophobic and one hydrophilic fragment. Such results suggest that two out of the six synthesized bis-furyl-pyrrolo[3,4-b]pyridin-5-ones derivatives presents potential antiviral activity against Dengue virus in vitro.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen. Una serie de seis bis-furil-pirrolo[3,4-b]piridin-5-onas sintetizadas vía una reacción Ugi-Zhu acoplada a un proceso en cascada [cicloadición aza Diels-Alder/N-acilación/aromatización] fueron evaluadas in vitro contra infección por el serotipo 4 del virus del dengue y el sistema de replicón del virus del Dengue que codifica un gen reportero de la luciferasa de la Renilla. Además, se realizaron estudios in silico sobre la proteína no estructural 3 (NS3), una proteasa de flavivirus que comprende un blanco atractivo para el desarrollo de antivirales terapéuticos unidos a la proteína no estructural 2B (NS3-NS2B). Los estudios in vitro revelaron que los compuestos 1a y 1b reducen la expresión de Renilla luciferasa en un 44.2 y 31.6%, respectivamente. Adicionalmente, estos compuestos redujeron la carga viral, revelando así su actividad potencial contra el virus del Dengue serotipo 4. Derivado de las simulaciones in silico, se obtuvo un modelo homólogo para NS3-NS2B, el cual fue considerado como blanco de las moléculas estudiadas. Los resultados computacionales correlacionan con los experimentales, mostrando que 1a es el mejor ligando. Finalmente, se generó un modelo farmacofórico para NS3-NS2B, el cual muestra que los ligandos necesitan dos fragmentos hidrofóbicos y uno hidrofílico. Estos resultados demuestran que dos de los seis compuestos que se estudiaron presentan actividad antiviral in vitro.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Dengue virus replicon]]></kwd>
<kwd lng="en"><![CDATA[dengue virus serotype 4]]></kwd>
<kwd lng="en"><![CDATA[in vitro assays]]></kwd>
<kwd lng="en"><![CDATA[in silico simulations]]></kwd>
<kwd lng="en"><![CDATA[docking]]></kwd>
<kwd lng="en"><![CDATA[pyrrolo[3,4-b]pyridin-5-ones]]></kwd>
<kwd lng="en"><![CDATA[Ugi-Zhu reaction]]></kwd>
<kwd lng="es"><![CDATA[Replicón del virus del dengue]]></kwd>
<kwd lng="es"><![CDATA[serotipo 4 del virus del dengue]]></kwd>
<kwd lng="es"><![CDATA[ensayos in vitro]]></kwd>
<kwd lng="es"><![CDATA[simulaciones in silico]]></kwd>
<kwd lng="es"><![CDATA[docking]]></kwd>
<kwd lng="es"><![CDATA[pirrolo[3,4-b]piridin-5-onas]]></kwd>
<kwd lng="es"><![CDATA[reacción de Ugi-Zhu]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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