<?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>0034-7418</journal-id>
<journal-title><![CDATA[Revista Colombiana de Ciencias Químico - Farmacéuticas]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. colomb. cienc. quim. farm.]]></abbrev-journal-title>
<issn>0034-7418</issn>
<publisher>
<publisher-name><![CDATA[Departamento de Farmácia, Facultad de Ciencias, Universidade Nacional da Colombia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0034-74182021000200505</article-id>
<article-id pub-id-type="doi">10.15446/rcciquifa.v50n2.92861</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Synthesis and antileishmanial activity of naphthoquinone-based hybrids]]></article-title>
<article-title xml:lang="es"><![CDATA[Síntesis y actividad antileishmania de híbridos naftoquinónicos]]></article-title>
<article-title xml:lang="pt"><![CDATA[Síntese e atividade antileishmania de híbridos naftoquinónicos]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Guimarães]]></surname>
<given-names><![CDATA[Délis Galvão]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Simplício]]></surname>
<given-names><![CDATA[Sidney Silva]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sousa]]></surname>
<given-names><![CDATA[Valéria Carlos de]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rodrigues]]></surname>
<given-names><![CDATA[Klinger Antonio da Franca]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Carvalho]]></surname>
<given-names><![CDATA[Fernando Aércio A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Carneiro]]></surname>
<given-names><![CDATA[Sabrina M. P.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Costa]]></surname>
<given-names><![CDATA[Marcília Pinheiro da]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gonsalves]]></surname>
<given-names><![CDATA[Arlan de A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Araújo]]></surname>
<given-names><![CDATA[Cleônia Roberta M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Federal University Rural of Pernambuco  ]]></institution>
<addr-line><![CDATA[Recife Pernambuco]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Federal University of San Francisco Valley  ]]></institution>
<addr-line><![CDATA[Petrolina Pernambuco]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Federal University of Piauí  ]]></institution>
<addr-line><![CDATA[Teresina Piauí]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Federal University of Parnaíba Delta  ]]></institution>
<addr-line><![CDATA[Parnaíba Piauí]]></addr-line>
<country>Brazil</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>08</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>08</month>
<year>2021</year>
</pub-date>
<volume>50</volume>
<numero>2</numero>
<fpage>505</fpage>
<lpage>521</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0034-74182021000200505&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0034-74182021000200505&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0034-74182021000200505&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[SUMMARY  Introduction: Leishmaniasis is a disease caused by protozoa of the genus Leishmania and is considered endemic in 98 countries. Treatment with pentavalent antimonials has a high toxicity, which motivates the search for effective and less toxic drugs. &#945;- and &#946;-lapachones have shown different biological activities, including antiprotozoa. In recent studies, the isonicotinoylhydrazone and phthalazinylhydrazone groups were considered innovative in the development of antileishmania drugs. Molecular hybridization is a strategy for the rational development of new prototypes, where the main compound is produced through the appropriate binding of pharmacophoric subunits.  Aims: To synthesize four hybrids of &#945;- and &#946;-lapachones, together with the isonicotinoylhydrazone and phthalazinylhydrazone groups and to determine the antileishmania activity against the promastigotic forms of L. amazonensis, L. infantum and L. major.  Results: &#946;-lapachone derivatives were more active against all tested leishmania species. &#946;ACIL (IC50 0.044&#956;M) and &#946;HDZ (IC50 0.023&#956;M) showed 15-fold higher activity than amphotericin B. The high selectivity index exhibited by the compounds indicates greater safety for vertebrate host cells.  Conclusion: The results of this work show that the hybrids &#946;ACIL and (3HDZ are promising molecules for the development of new antileishmania drugs.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Introducción: Leishmaniasis es una enfermedad causada por protozoos del género Leishmania y se considera endémica en 98 países. El tratamiento con antimoniales pentavalentes tiene una alta toxicidad, lo que motiva la búsqueda de fármacos eficaces y menos tóxico. &#945;- y &#946;-lapachones han mostrado diferentes actividades biológicas, incluido los antiprotozoarios. En estudios recientes, los grupos isonicotinoilhidra-zona y ftalazinilhidrazona se consideraron innovadores en el desarrollo de fármacos antileishmania. La hibridación molecular es una estrategia para el desarrollo racional de nuevos prototipos, donde el compuesto principal se produce a través de la unión apropiada de subunidades farmacofóricas.  Objetivos: Sintetizar cuatro híbridos de &#945;- y &#946;-lapachones, junto con los grupos isonicotinoilhidrazona y ftalazinilhidrazona y determinar la actividad antileishmania frente a las formas promastigotas de L. amazonensis, L. infantum y L. major.  Resultados: Los derivados de &#946;-lapachone fueron más activos contra todas las especies de leishmania probadas. La &#946;ACIL (CI50 0,044&#956;M) y &#946;HDZ (CI50 0,023&#956;M) mostraron actividad 15 veces mayor que la anfotericina B. El alto índice de selectividad que presentan los compuestos indica una mayor seguridad para las células huésped del vertebrado.  Conclusión: Los resultados de este trabajo demuestran que los híbridos (ACIL y (HDZ son moléculas prometodoras para el desarrollo de nuevos fármacos antileishmania.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[RESUMO  Introdução: A leishmaniose é uma doença causada por protozoários do género Leishmania e é considerada endémica em 98 países. O tratamento com antimoniais pentavalentes apresenta alta toxicidade, o que motiva a pesquisa por medicamentos eficazes e menos tóxicos. &#945;- e &#946;-lapachones tém mostrado diferentes atividades biológicas, incluindo antiprotozoários. Em estudos recentes, os grupos isonicotinoilhi-drazona e ftalazinilhidrazona foram considerados inovadores no desenvolvimento de drogas antileishmania. A hibridização molecular é uma estratégia para o desenvolvimento racional de novos protótipos, onde o composto principal é produzido através da ligação apropriada de subunidades farmacofóricas.  Objetivos: Sintetizar quatro híbridos de &#945;- e &#946;-lapachones, juntamente com os grupos isonicotinoil-hidra-zona e ftalazinilhidrazona e determinar a atividade antileishmania contra as formas promastigóticas de L. amazonensis, L. infantum e L. major.  Resultados: Os derivados de &#946;-lapachona foram mais ativos contra todas as espécies de leishmania testadas. BACIL (IC50 0,044 &#956;M) e &#946;HDZ (IC50 0,023 &#956;M) apresentaram atividade 15 vezes maior do que a anfotericina B. O alto índice de seletividade dos compostos indica maior segurança para células hospedeiras de vertebrados.  Conclusaõ: Os resultados deste trabalho mostram que os híbridos &#946;ACIL e &#946;HDZ são moléculas promissoras para o desenvolvimento de novos fármacos antileishmania.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[&#946;lapachone]]></kwd>
<kwd lng="en"><![CDATA[&#945;-lapachone]]></kwd>
<kwd lng="en"><![CDATA[molecular hybridization]]></kwd>
<kwd lng="en"><![CDATA[hydralazine]]></kwd>
<kwd lng="en"><![CDATA[isoniazid]]></kwd>
<kwd lng="en"><![CDATA[hydrazone]]></kwd>
<kwd lng="es"><![CDATA[&#946;-lapachone]]></kwd>
<kwd lng="es"><![CDATA[&#945;-lapachone]]></kwd>
<kwd lng="es"><![CDATA[hibridación molecular]]></kwd>
<kwd lng="es"><![CDATA[hidralazina]]></kwd>
<kwd lng="es"><![CDATA[isoniazida]]></kwd>
<kwd lng="es"><![CDATA[hidrazona]]></kwd>
<kwd lng="pt"><![CDATA[&#946;-lapachona]]></kwd>
<kwd lng="pt"><![CDATA[&#945;-lapachona]]></kwd>
<kwd lng="pt"><![CDATA[hibridização molecular]]></kwd>
<kwd lng="pt"><![CDATA[hidralazina]]></kwd>
<kwd lng="pt"><![CDATA[isoniazida]]></kwd>
<kwd lng="pt"><![CDATA[hidrazona]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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