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                <text>Bioorganic and Medicinal Chemistry v.17, 2009. -- p.641-652</text>
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                <text>The synthesis and characterization of the first two Re complexes with semicarbazone ligands is presented. Selected ligands are 5-Nitro-2-furaldehyde semicarbazone (Nitrofurazone) (L1) and its derivative 3-(5-Nitrofuryl)acroleine semicarbazone (L2). Complexes of general formula [ReVOCl2(PPh3)L], where L � L1 and L2, were prepared in good yields and high purity by reaction of [ReVOCl3(PPh3)2] with L in ethanol or methanol solutions. The complexes formula and molecular structures were supported by elemental analyses and electronic, FTIR, 1H, 13C and 31P NMR spectroscopies. In addition, the crystal and molecular structure of [ReVOCl2(PPh3)L2] was determined by X-ray diffraction methods. [ReOCl2(PPh3)(3-(5-Nitrofuryl)acroleine semicarbazone)] crystallizes in the space group P-1 with a � 11.2334(2), b � 11.3040(2), c � 12.5040(2) A &amp;deg; , &amp;alpha; � 81.861(1), &amp;beta; � 63.555(1), &amp;gamma; � 83.626(1)&amp;deg;, and Z � 2. The Re(V) ion is in a distorted octahedral environment, equatorially coordinated to a deprotonated semicarbazone molecule acting as a bidentate ligand through its carbonylic oxygen and azomethynic nitrogen atoms, to an oxo ligand and a chlorine atom. The six-fold coordination is completed by another chlorine atom and a triphenylphosphine ligand at the axial positions.</text>
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                <text>&lt;p&gt;An important issue in the development of metal-based radiopharmaceuticals is the selection of the labelling strategy in order to couple the metal to the pharmacophore without losing the biological activity. With the aim to evaluate the correlation between ligand denticity and biological behaviour of the corresponding 99mTc complexes, we designed a tridentate and a bidentate 5-nitroimidazole derivatives suitable for 99mTc(I) tricarbonyl complexation and with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis. Ligands were synthesized using metronidazol, a pharmaceutical containing the bioreductive pharmacophore as starting material. The chelating units were connected to the pharmacophore using the click reaction of Huisgen. Both 99mTc complexes were obtained in high yield and were hydrophilic and stable in labelling milieu. The complex obtained from the tridentate ligand exhibited high stability in human plasma, low protein binding and a favourable biodistribution characterized by low blood and liver uptake, fast elimination and negligible uptake in other organs or tissues. Selective uptake and retention in tumour together with favourable tumour/muscle ratio makes this 99mTc-complex a promising candidate for further evaluation as potential hypoxia imaging agent in tumours. The bidentate ligand, on the other hand, yielded a less stable 99mTc-complex that experimented hydrolysis in vitro and decomposition in human plasma and showed high protein binding, high blood and liver uptake and moderate excretion. Although selective uptake and retention in tumour was also observed physicochemical and biological behaviour are inadequate for in vivo use, demonstrating that denticity of the ligand is particularly important and that tridentate ligands are preferable in order to prepare 99mTc-tricarbonyl complexes for Nuclear Medicine imaging&lt;/p&gt;</text>
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&lt;p&gt;(Por favor lea este aviso antes de abrir los documentos u objetos)&lt;/p&gt;&#13;
&lt;p&gt;&lt;strong&gt;La legislaci&amp;oacute;n uruguaya&lt;/strong&gt; protege el derecho de autor sobre toda creaci&amp;oacute;n literaria, cient&amp;iacute;fica o art&amp;iacute;stica, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeci&amp;oacute;n a lo establecido por el derecho com&amp;uacute;n y las siguientes leyes&lt;/p&gt;&#13;
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&lt;p style="margin-bottom: 0cm;"&gt;&lt;strong&gt;ADVERTENCIA&lt;/strong&gt; - La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;&#13;
&lt;p&gt;&lt;br /&gt;&lt;br /&gt;&lt;/p&gt;&#13;
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                <text>Context: Triosephosphate isomerase (TIM) is a ubiquitous enzyme that has been targeted for the discovery of small molecular weight compounds with potential use against Trypanosoma cruzi, the causative agent of Chagas disease. We have identified a new selective inhibitor chemotype of TIM from T. cruzi (TcTIM), 1,2,4-thiadiazol-5(4H)-one. Objective: Study the mechanism of TcTIM inhibition by a 1,2,4-thiadiazol derivative. Methods: We performed the biochemical characterization of the interaction of the 1,2,4-thiadiazol derivative with the wild-type and mutant TcTIMs, using DOSY-NMR and MS experiments. Studies of T. cruzi growth inhibition were additionally carried out. Results and conclusion: At low micromolar concentrations, the compound induces highly selective irreversible inactivation of TcTIM through non-covalent binding. Our studies indicate that it interferes with the association of the two monomers of the dimeric enzyme. We also show that it inhibits T. cruzi growth in culture</text>
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&lt;p&gt;&lt;strong&gt;La legislaci&amp;oacute;n uruguaya&lt;/strong&gt; protege el derecho de autor sobre toda creaci&amp;oacute;n literaria, cient&amp;iacute;fica o art&amp;iacute;stica, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeci&amp;oacute;n a lo establecido por el derecho com&amp;uacute;n y las siguientes leyes&lt;/p&gt;&#13;
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&lt;p&gt;&lt;strong&gt;ADVERTENCIA&lt;/strong&gt; - La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;&#13;
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                <text>Introduction: Quinoxaline scaffold is included in a large number of therapeutic agents because of its physicochemical properties that make the difference between them and the carbono analogue, naphthalene. Areas covered: This review of patented products presents the quinoxaline 10 heterocycle as part of the structural patent claims from a medicinal chemistry perspective. Expert opinion: We centred our discussion in the various drug patent applications of the quinoxaline and its derivatives. The applications are based firstly in the specific enzyme target with very low development in the disease 15 treatment. Only for cancer and antimicrobial agents they were specifically determined but little is mentioned in order to insight in the last development activities.</text>
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                <text>Expert Opinion on Therapeutic Patents . v.12, no. 11, 2012. -- p.1289-1302</text>
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                <text>&lt;p&gt;&lt;strong&gt;Informaci&amp;oacute;n sobre Derechos de Autor&lt;/strong&gt;&lt;/p&gt;&#13;
&lt;p&gt;(Por favor lea este aviso antes de abrir los documentos u objetos)&lt;/p&gt;&#13;
&lt;p&gt;&lt;strong&gt;La legislaci&amp;oacute;n uruguaya&lt;/strong&gt; protege el derecho de autor sobre toda creaci&amp;oacute;n literaria, cient&amp;iacute;fica o art&amp;iacute;stica, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeci&amp;oacute;n a lo establecido por el derecho com&amp;uacute;n y las siguientes leyes&lt;/p&gt;&#13;
&lt;p&gt;(LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)&lt;/p&gt;&#13;
&lt;p&gt;&lt;strong&gt;ADVERTENCIA&lt;/strong&gt; - La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;&#13;
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                <text>Exploring the influence of different substitution patterns of 2H-benzimidazole 1,3-dioxide derivatives (BzNO) we prepared fifteen new derivatives. Initially the BzNO were tested against Trypanosoma cruzi Tulahuen 2 strain epimastigote form rendering very potent anti-T. cruzi agents. Moreover, the BzNO were able to inhibit the growth of virulent and resistant to Benznidazole strains (CL Brener clone, Colombiana, and Y strains) and to Leishmania braziliensis. Interestingly, BzNO exhibited very high selectivity index and particularly the spiro-BzNO 13 provokes an important diminution of amastigotes in Vero cells. Besides, it was found a diminution of acetate and glycine as excreted metabolites but without increase of parasite glucose uptake indicating that the glycosome is probably not involucrate in the 2H-benzimidazole 1,3- dioxides mechanism of action</text>
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&lt;p&gt;&lt;strong&gt;ADVERTENCIA -&lt;/strong&gt; La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;</text>
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&lt;p&gt;&lt;strong&gt;ADVERTENCIA -&lt;/strong&gt; La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;</text>
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                <text>Chagas&amp;rsquo; disease is the major endemic disease in South and Central America caused by a trypanosomatid parasite (Trypanosoma cruzi). The current treatment relies on two old and nonspecific chemotherapeutic agents, Nifurtimox and Benznidazole. Despite the major advances that have been made in the identification of specific targets that afford selectivity, the drugs used today have serious side effects. Furthermore, differences in drug susceptibility among different T. cruzi isolates have led to varied parasitological cure rates depending on the geographical region. There is, therefore, an urgent need for the development of new antichagasic drugs. In this regard we have spent more than a decade in the search for more effective agents able to compromise the proliferation of T. cruzi. We began our research with our own compounds and then continued with compounds from other researcher groups. We systematically characterized representatives of a wide range of different chemical families. In this review we summarize our ongoing efforts to identify potential anti-T. cruzi agents using our compound-library. It is discussed and presented the structure- activity relationship observed among the different groups of chemical families.</text>
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&lt;p&gt;&lt;strong&gt;ADVERTENCIA&lt;/strong&gt; - La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;&#13;
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                <text>Since the middle of the 20th century, benzofuroxan and furoxan derivatives have been extensively studied as bioactive compounds. Maybe the most relevant reported biological property has been related to its capability to release nitric oxide; moreover, other significant activities have been identified, such as antibacterial, antifungal, antiparasite, cytotoxic, and herbicide properties. Recently, research and development in the medicinal chemistry field of these systems have produced hybrid compounds in which benzofuroxanyl or furoxanyl moieties together with classical drug moieties are present in a single molecule. Consequently, new anti-ulcer drugs, calcium channel modulators, vasodilator derivatives, antioxidants, among others, have been described and are currently under study. On the other hand, these kinds of compounds have also been reported as components in primary explosives, polymers, and propellants. This chapter includes older as well as more recent methods of synthesis of benzofuroxan and furoxan derivatives, chemical and biological reactivity, biological properties and mode of action, structure-activity studies and other relevant chemical and biological propert</text>
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                <text>Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy v. 70A, no. 3, 2008. -- p.519-523</text>
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                <text>The development of hybrid compounds containing limonene- and recognized anti-T. cruzi-heterocycleframeworks is described. The six new compounds displayed broad antitrypanosomal activities having 5-nitrofuran and 5- nitroindazole derivatives, the best profiles. In addition, a 5-nitroindazole derivative evaluated against a panel of fungi exhibited relevant activities. Knowing that free-radical-production operates as one of the mechanisms of action on these heterocycles, we studied a potential extra-mechanism, membrane-sterols changes. Non-relevant T. cruzi squalene accumulation was observed for any of the tested hybrid-limonene derivatives.</text>
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&lt;p&gt;&lt;strong&gt;La legislaci&amp;oacute;n uruguaya&lt;/strong&gt; protege el derecho de autor sobre toda creaci&amp;oacute;n literaria, cient&amp;iacute;fica o art&amp;iacute;stica, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeci&amp;oacute;n a lo establecido por el derecho com&amp;uacute;n y las siguientes leyes&lt;/p&gt;&#13;
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&lt;p&gt;&lt;strong&gt;ADVERTENCIA&lt;/strong&gt; - La consulta de este documento queda condicionada a la aceptaci&amp;oacute;n de las siguientes condiciones de uso: Este documento es &amp;uacute;nicamente para usos privados enmarcados en actividades de investigaci&amp;oacute;n y docencia. No se autoriza su reproducci&amp;oacute;n con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilizaci&amp;oacute;n o cita de partes debe indicarse el nombre de la persona autora.&lt;/p&gt;</text>
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