Chagas

chagas

THE DISEASEPREVALENCE TREATMENT LINES OF RESEARCHRESEARCH TEAMPUBLICATIONS

The disease

CD is caused by the protozoan parasite Trypanosome cruzi. The main transmission routes are:

  • Bites and faeces of Triatominae insect, known as kissing bugs, bed bugs and other names based on geographic area.

  • Food contaminated with the parasite.

  • Transfusions of infected blood.

  • Transmission from the infected mother to the child during pregnancy or childbirth.

  • Transplantation of organs from an infected donor.

  • Laboratory accidents

Prevalence

The World Health Organization (WHO) estimates that 7 to 8 million people are infected with CD worldwide. Approximately 200 thousand appear every year, and 21 thousand deaths are caused. It mainly affects developing countries especially in Latin America, but in recent decades it has been observed in developed countries like the United States, Canada, European countries and some West Pacific Countries. This makes CD a disease of global public health. 

Treatment

There are only two drugs, nifurtimox and benznidazole. Both have significant toxic effects and relative clinical efficacy. The pharmacotherapy of the CD is therefore very poor, urging the development of safe and effective new medicines

Lines of research

We are an International Working Group with extensive research experience in the fight against CD. Our efforts are focused on discovering new molecules of low cost and non complex synthesis, with activity against the agent causing this disease. We are dedicated to designing these molecules and the structural elucidation of compounds synthesized by H1-NMR, C13-NMR, 2D-NMR, elemental analysis, HPLC and mass spectrometry techniques.

We have discovered the potential of Quinoxalines as potential antichagasic agents, allowing us to introduce a patent with Laboratories Silanes (Mexico). Our great challenge is to create a treatment that ends with CD.

Institutions we collaborate with:

  • Laboratories Silanes (México) (Silanes Laboratories Mexico)

  • Universidad Federal de Rio de Janeiro, Brazil (Federal University of  Rio de Janeiro, Brazil)

  • Grupo de Química Medicinal de la Universidad de la República, Montevideo, Uruguay (Medicinal Chemistry Group Republic University, Montevideo, Uruguay)

  • Grupo de Medicina Tropical, Universidad Nacional de Asunción, Paraguay (Tropical Medicine Group, National University of Asunción, Paraguay)

  • Dundee University. United Kingdom

Research Team

Publications

Elsa Moreno-Viguri, Silvia Pérez-Silanes. Quinoxaline 1,4-di-N-oxide derivatives: Interest in the treatment of Chagas Disease. Revista Virtual de Química.  (Virtual Chemistry Journal) 2013, 5, 1101-1119.

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Enrique Torres, Elsa Moreno-Viguri, Silvia Galiano, Goutham Devarapally, Philip W. Crawford, Amaia Azqueta, Leire Arbillaga, Hugo Cerecetto, Mercedes González, Ignacio Aldana, Antonio Monge, Silvia Pérez-Silanes Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents. European Journal of Medical Chemistry. 2013, 66, 324-334. (Impact Factor: 3.432; Revista 13 de 58 en Química Médica). (Medical Chemistry Journal 13 of 58)

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Silvia Pérez-Silanes, Goutham Devarapally, Enrique Torres, Elsa Moreno-Viguri, Ignacio Aldana, Antonio Monge and Philip W. Crawford. Voltammetric Study of Some Anti-Chagas Active Quinoxaline 1,4-Di-N-Oxide-2-Ketone Derivatives. Helvetica Chimica Acta. 2013, 96, 217-227. (Impact Factor: 1.394; Revista 75 de 148 en Química Multidisciplinar) (Multidisciplinary Chemistry Journal 75 of 148)

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3-TRIFLUOROMETHYLQUINOXALINE N,N'-DIOXIDES AS ANTI-TRYPANOSOMATID AGENTS. IDENTIFICATION OF OPTIMAL ANTI-T. CRUZI AGENTS AND MECHANISM OF ACTION STUDIES.
Benitez D, Cabrera M, Hernández P, Boiani L, Lavaggi ML, Di Maio R, Yaluff G, Serna E, Torres S, Ferreira ME, Vera de Bilbao N, Torres E, Pérez-Silanes S, Solano B, Moreno E, Aldana I, López de Ceráin A, Cerecetto H, González M, Monge A.  J Med Chem. 2011 May 26;54(10):3624-3636. Epub 2011 May 4.
PUBMED COURTESY ABSTRACT.

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DERIVADOS DE QUINOXALINA SELECTIVOS CONTRA TRYPANOSOMA CRUZI Y QUE NO CAUSAN EFECTOS MUTAGÉNICOS.
A. Monge, S. Pérez Silanes, I. Aldana, E. Moreno, E. Torres, H. Cerecetto Meyer, M. M. González Hormaizteruy and J. F. Paniagua Solís. Patente solicitada en México el 11 de enero de 2011 y Extensión internacional de la patente solicitada en Ginebra el 9 de marzo de 2011. Nº PCT/MX/2001/000006

(SELECTIVE QUINOXALINE DERIVATIVES AGAINST TRYPANOSOMA CRUZI THAT DO NOT CAUSE MUTAGENIC EFFECTS.
A. Monge, S. Pérez Silanes, I. Aldana, E. Moreno, E. Torres, H. Cerecetto Meyer, M. M. González Hormaizteruy and J. F. Paniagua Solis. Patent requested in Mexico on January 11, 2011 and international Extension of the patent requested in Geneva on March 9, 2011. Nº PCT/MX/2001/000006)

 

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ANTI-T. CRUZI ACTIVITIES AND QSAR STUDIES OF 3-ARYLQUINOXALINE-2-CARBONITRILE DI-N-OXIDES.
Vicente E, Duchowicz PR, Benítez D, Castro EA, Cerecetto H, González M, Monge A. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4831-5. Epub 2010 Jun 25.
ABSTRACT PUBMED COURTESY.

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CYTOTOXIC, MUTAGENIC AND GENOTOXIC EFFECTS OF NEW ANTI-T. CRUZI 5-PHENYLETHENYLBENZOFUROXANS. CONTRIBUTION OF PHASE I METABOLITES ON THE MUTAGENICITY INDUCTION.
Cabrera M, Lavaggi ML, Hernández P, Merlino A, Gerpe A, Porcal W, Boiani M, Ferreira A, Monge A, de Cerain AL, González M, Cerecetto H. Toxicol Lett. 2009 Oct 28;190(2):140-9. Epub 2009 Jul 10.
ABSTRACT PUBMED COURTESY.

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NEW THERAPEUTIC TARGETS FOR DRUG DESIGN AGAINST TRYPANOSOMA CRUZI, ADVANCES AND PERSPECTIVES.
Rivera G, Bocanegra-García V, Ordaz-Pichardo C, Nogueda-Torres B, Monge A. Curr Med Chem. 2009;16(25):3286-93. Epub 2009 Sep 1. Review.
ABSTRACT PUBMED COURTESY.

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HETEROCYCLIC-2-CARBOXYLIC ACID (3-CYANO-1,4-DI-N-OXIDEQUINOXALIN-2-YL)AMIDE DERIVATIVES AS HITS FOR THE DEVELOPMENT OF NEGLECTED DISEASE DRUGS.
Ancizu S, Moreno E, Torres E, Burguete A, Pérez-Silanes S, Benítez D, Villar R, Solano B, Marín A, Aldana I, Cerecetto H, González M, Monge A. Molecules. 2009 Jun 22;14(6):2256-72.
ABSTRACT PUBMED COURTESY
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SYNTHESIS, TRYPANOCIDAL ACTIVITY AND DOCKING STUDIES OF NOVEL QUINOXALINE-N-ACYLHYDRAZONES, DESIGNED AS CRUZAIN INHIBITORS CANDIDATES.
Romeiro NC, Aguirre G, Hernández P, González M, Cerecetto H, Aldana I, Pérez-Silanes S, Monge A, Barreiro EJ, Lima LM. Bioorg Med Chem. 2009 Jan 15;17(2):641-52. Epub 2008 Dec 3.
ABSTRACT PUBMED COURTESY.

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IMPROVING ANTI-TRYPANOSOMAL ACTIVITY OF 3-AMINOQUINOXALINE-2-CARBONITRILE N1,N4-DIOXIDE DERIVATIVES BY COMPLEXATION WITH VANADIUM.
Urquiola C, Vieites M, Aguirre G, Marín A, Solano B, Arrambide G, Noblía P, Lavaggi ML, Torre MH, González M, Monge A, Gambino D, Cerecetto H. Bioorg Med Chem. 2006 Aug 15;14(16):5503-9. Epub 2006 May 18.
ABSTRACT PUBMED COURTESY.

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INDAZOLE N-OXIDE DERIVATIVES AS ANTIPROTOZOAL AGENTS: SYNTHESIS, BIOLOGICAL EVALUATION AND MECHANISM OF ACTION STUDIES.
Gerpe A, Aguirre G, Boiani L, Cerecetto H, González M, Olea-Azar C, Rigol C, Maya JD, Morello A, Piro OE, Arán VJ, Azqueta A, de Ceráin AL, Monge A, Rojas MA, Yaluff G. Bioorg Med Chem. 2006 May 15;14(10):3467-80. Epub 2006 Feb 17.
ABSTRACT PUBMED COURTESY.

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BENZO[1,2-C]1,2,5-OXADIAZOLE N-OXIDE DERIVATIVES AS POTENTIAL ANTITRYPANOSOMAL DRUGS. STRUCTURE-ACTIVITY RELATIONSHIPS. PART II.
Aguirre G, Cerecetto H, Di Maio R, González M, Porcal W, Seoane G, Ortega MA, Aldana I, Monge A, Denicola A. Arch Pharm (Weinheim). 2002 Jan;335(1):15-21.
ABSTRACT PUBMED COURTESY.