Aldana, I. (Ignacio)

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    Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents
    (Elsevier, 2013-05-30) Devarapally, G. (Goutham); Aldana, I. (Ignacio); Torres, E. (Enrique); Gonzalez, M. (Mercedes); Varela, J. (Javier); Di-Maio, R. (Rossanna); Birriel, E. (Estefanía); Arbillaga, L. (Leire); Pérez-Silanes, S. (Silvia); Galiano, S. (Silvia); Monge, A. (Antonio); Moreno-de-Viguri, E. (Elsa); Cerecetto, H. (Hugo); Azqueta, A. (Amaya); Crawford, P.W. (Philip W.)
    As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-Noxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with fluoro groups at the 6- and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups,possessed a greater ease of reduction of the N-oxide groups
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    New amide derivatives of quinoxaline 1,4-di-N-oxide with leishmanicidal and antiplasmodial activities
    (MDPI, 2013) Aldana, I. (Ignacio); Deharo, E. (Eric); Pabon, A. (Adriana); Pérez-Silanes, S. (Silvia); Galiano, S. (Silvia); Monge, A. (Antonio); Barea, C. (Carlos); Gonzalez, G. (Germán)
    Malaria and leishmaniasis are two of the World’s most important tropical parasitic diseases. Continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-N-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum FCR-3 strain, Leishmania infantum and Leishmania amazonensis. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. The results obtained indicate that a cyclopentyl derivative had the best antiplasmodial activity (2.9 µM), while a cyclohexyl derivative (2.5 µM) showed the best activity against L. amazonensis, and a 3-chloropropyl derivative (0.7 µM) showed the best results against L. infantum. All these compounds also have a Cl substituent in the R7 position.
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    Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents
    (Wiley-Blackwell, 2011) Pontiki, E. (Eleni); Aldana, I. (Ignacio); Ancizu, S. (Saioa); Torres, E. (Enrique); Burguete, A. (Asunción); Pérez-Silanes, S. (Silvia); Monge, A. (Antonio); Moreno-de-Viguri, E. (Elsa); Solano, B. (Beatriz); Raquel; Hadjipavlou-Litina, D. (Dimitra)
    We report the synthesis, anti-inflammatory and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave assisted methods have been used in order to optimize reaction times and to improve the yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase. Two of the best lipoxygenase inhibitors (compounds 7b and 8f) were evaluated as in vivo anti-inflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug.
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    New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities
    (Elsevier, 2011) Quiliano, M. (Miguel); Aldana, I. (Ignacio); Deharo, E. (Eric); Zimic, M. (Mirko); Pabon, A. (Adriana); Pérez-Silanes, S. (Silvia); Galiano, S. (Silvia); Monge, A. (Antonio); Barea, C. (Carlos); Castillo, D. (Denis)
    Continuing with our efforts to identify new active compounds against malaria and leishmaniasis, fourteen new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies were carried out in order to analyze graphic SAR and ADME properties. The results obtained indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found
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    New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities
    (Elsevier, 2011) Aldana, I. (Ignacio); Deharo, E. (Eric); Zimic, M. (Mirko); Pabon, A. (Adriana); Pérez-Silanes, S. (Silvia); Galiano, S. (Silvia); Monge, A. (Antonio); Barea, C. (Carlos); Castillo, D. (Denis)
    Continuing with the efforts to identify new active compounds against malaria and leishmaniasis, fourteen new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies to analyze graphic SAR and ADME properties were undertaken. Results indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found
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    Derivados de 1,4-di-N-óxido de quinoxalina y enfermedades olvidadas
    (Real Academia de Farmacia, 2007) Aldana, I. (Ignacio); Ancizu, S. (Saioa); Vicente, E. (Esther); Burguete, A. (Asunción); Pérez-Silanes, S. (Silvia); Monge, A. (Antonio); Solano, B. (Beatriz); Raquel
    Las enfermedades olvidadas son un grupo de enfermedades infecciosas médicamente diversas entre las que se encuentran tuberculosis, malaria, leishmaniasis y la enfermedad de Chagas, que afectan a millares de personas en todo el mundo pero, principalmente, a la gente pobre en países en vías de desarrollo. Son un reto para la Salud Pública Internacional ya que no existen vacunas parar controlarlas y los medicamentos existentes para su tratamiento no son adecuados. La necesidad de buscar nuevas terapias económicamente accesibles para la población afectada es cada vez más urgente y palpable, lo que ha dado lugar a la puesta en marcha de nuevas iniciativas internacionales que buscan la erradicación de estas enfermedades. A lo largo de los años, nuestro grupo de investigación ha llevado a cabo el diseño y la síntesis, mediante métodos sintéticos sencillos y de bajo coste, de diversos derivados de 1,4-di-N-óxido de quinoxalina con el objetivo de encontrar nuevos líderes para el tratamiento de algunas enfermedades olvidadas. Como resultado de varios proyectos de investigación, se han desarrollado nuevas estructuras activas como agentes antituberculosos, antimaláricos, antichagas y, más recientemente, como agentes antileishmania. Este resumen presenta los resultados más importantes obtenidos en este campo, de los que se puede concluir que el núcleo de 1,4-di-N-óxido de quinoxalina representa un posible avance en la búsqueda de nuevos compuestos activos.
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    Studies on LogP o/w of Quinoxaline di-N-osides: a comparison of RP-HPLC experimental and predictive approaches
    (MDPI, 2011-09-13) Aldana, I. (Ignacio); Gabano, E. (Elisabetta); Pérez-Silanes, S. (Silvia); Monge, A. (Antonio); Moreno-de-Viguri, E. (Elsa); Ravera, M. (Mauro); Platts, J.A. (James A.)
    As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We found that the prediction of log P by the RP-HPLC analysis can result in a high accuracy and can replace the shake-flask method avoiding the experimental problems presented by quinoxaline di-N-oxides. The studied compounds were subjected to the ALOGPS module with the aim of comparing experimental log Po/w values and predicted data. Moreover, a preliminary in silico screening of the QSAR relationship was made confirming the influence of reduction peak potential, lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti-tuberculosis activity.
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    New antagonist agents of Neuropeptide Y receptors
    (Sociedade Brasileira de Química, 2000) Huenchuñir, P. (Patricio); Alonso, M.L. (María Luisa); Aldana, I. (Ignacio); Frigola, C. (Carmen); Rivero, I. (Isabel); Monge, A. (Antonio); Rivero, A. (Argimiro)
    In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists mill be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.
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    Unexpected reduction of ethyl 3-phenylquinoxaline-2- carboxylate 1,4-di-N-oxide derivatives by amines.
    (MDPI, 2008) Lima, L.M. (Lidia M.); Aldana, I. (Ignacio); Vicente, E. (Esther); Pérez-Silanes, S. (Silvia); Monge, A. (Antonio); Solano, B. (Beatriz)
    The unexpected tendency of amines and functionalized hydrazines to reduce ethyl 3-phenylquinoxaline-2-carboxylate 1,4-di-N-oxide (1) to afford a quinoxaline 1c and mono-oxide quinoxalines 1a and 1b is described. The experimental conditions were standardized to the use of two equivalents of amine in ethanol under reflux for two hours, with the aim of studying the distinct reductive profiles of the amines and the chemoselectivity of the process. With the exception of hydrazine hydrate, which reduced compound 1 to a 3-phenyl-2-quinoxalinecarbohydrazide derivative, the amines only acted as reducing agents.
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    Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies
    (Elsevier, 2012) Aldana, I. (Ignacio); Ceras, J. (Javier); Pérez-Silanes, S. (Silvia); Galiano, S. (Silvia); Monge, A. (Antonio); Cirauqui, N. (Nuria)
    The combination of antagonism at histamine H3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H3 antagonism affinity. However, since all these derivatives failed to block KATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype.