Malaria

THE DISEASEPREVALENCE TREATMENT LINES OF RESEARCHRESEARCH TEAMPUBLICATIONSCOLABORATIONS

THE DISEASE

Malaria  is caused by four species of Plasmodium parasite (falciparum, vivax, ovale and malarie). The parasite infects humans through a mosquito Anopheles bite, mosquitoes maintain the cycle by feeding on infected patients. 

Prevalence

Closely linked to poverty, malaria remains one of the major public health challenges worldwide. The WHO estimates that in 2012 there were 219 million new cases and 627.000 annual deaths, mainly at the most disadvantaged populations in sub-Saharan Africa. Children under five years of age are the most affected.

TREATMENT

Malaria has developed resistance to the drugs that have been used for years, such as chloroquine or sulfadoxine-pyrimethamine. Currently the most effective treatments are therapies combined with artemisinin (TCA). This combination is used to extend and reinforce the treatment effect and delay the onset of resistance. Failure in the development of effective insecticides against the mosquito and the fact that vaccines still continue under development entails an urgent need to develop new pharmacological therapies with improved safety and efficacy profiles.

Lines of research

  • 1. Vector control

    The fight against the mosquito is a cornerstone in the antimalaric battle. The emergence of insecticide resistance and the adaptation of the behaviour of the mosquito vector make the usual control measures (such as mosquito nets and residual insecticides) less effective.

    It is necessary to develop new methods capable of fighting the mosquito, even if it feeds outdoors or at twilight. Ivermectin is a safe drug, capable of killing the mosquitoes that feed on treated patients, independently of place or time of the day.

    The MISSION project aims to develop a an ivermectin extended-release system to maintain plasma levels high enough to kill mosquitoes safely, long enough to have a significant impact on malaria transmission. 

  • 2. Compounds

    Our research group has always had a special relationship with tropical diseases and has been working for many years on the design and synthesis of several derivatives in the means of finding new leaders for the treatment of theses diseases in general and Malaria in particular, obtaining excellent results from this activity.

    The main objective of this project is to find new leaders to fight malaria with a high antimalarial strength and low toxicity based on the synthesis of two proposed series heads: new hybrids of chloroquine/primaquine and quinoxaline 1, 4-di-N-oxide and arilaminoalcoholes. The strategy is to design in silico, synthesis and biological evaluation in vitro and in vivo of new derivates against strains of cloroquine-sensitive (3D7) and cloroquine-resistant (FCR3) p.falciparum. From these biological findings, will be carried out studies of docking and QSAR and structure-activity relations of more active compounds that will allow us to identify the leaders, optimizing the first hypothesis and redesigning new analogues according to the strength and ADMET properties of derivatives. One of the great challenges of this project is to discover the mechanism of action of these compounds through the identification of therapeutic targets with Proteomics studies.

"Medical Chemistry" Research team

"Vector Control" Research Team

  • José Luis del Pozo (MED, PhD) José Luis del Pozo (MED, PhD)
    Principal Investigator
    Telephone: +34 948 255 400 Email: jdelpozo@unav.es
  • Carlos Chaccour MED Carlos Chaccour MED
    Principal Investigator
    Telephone: +34 948 255 400 Extension:
    Curriculum Vitae (.pdf)
    Email: cchaccour@unav.es
  • Ana Gloria Gil-Royo (PhD) Ana Gloria Gil-Royo (PhD)
    PhD
    Telephone: + 34 948 425600 Email: agil@unav.es
  • Elena González-Peñas (PhD) Elena González-Peñas (PhD)
    PhD
    Telephone: + 34 948 425600
  • Ángel Irigoyen Ángel Irigoyen
    Investigator and PhD Student
    Telephone: + 34 948 425600

Publications

Publications of the Malaria "Vector Control" research team

"Oral, Slow-Release Ivermectin: Biting Back at Malaria Vectors"
Chaccour CJ1, Rabinovich NR2.
More information

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Slow Release Ivermectin Formulation for Malaria Control: a Pilot Study in 80-kg Pigs.
Chaccour C1,2, Abizanda G3, Irigoyen Á4, Del Pozo JL5.
More information

 

Publications of the Malaria "Medical Chemistry" research team

"New arylaminoalcohol derivatives with antiplasmodial activity". I. Aldana, S. Blair, E. Deharo, S. Galiano, G. Garavito, A. Mendoza, S. Pérez-Silanes. Patente solicitada el 15 de marzo de 2014. PCT/IB2014/059803 (Patent solicited on March 15th 2014)

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Carlos Barea, Adriana Pabón, Silvia Pérez-Silanes, Silvia Galiano, Germán González, Antonio Monge, Eric Deharo, Ignacio Aldana. "New amide derivatives of quinoxaline 1,4-di-N-oxide with leishmanicidal and antiplasmodial activities". Molecules 2013, 18: 4718-4727.

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Carlos Barea, Adriana Pabón, Silvia Galiano, Silvia Pérez-Silanes, Germán González, Chloe Deyssard, Antonio Monge, Eric Deharo, Ignacio Aldana. "Antiplasmodial and leishmanicidal activities of 2-cyano-3-(4-phenylpiperazine-1-carboxamido)quinoxaline 1,4-dioxide derivatives".
Molecules 2012, 17: 9451-9461.

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Carlos Barea, Adriana Pabón, Denis Castillo, Mirko Zimic, Miguel Quiliano, Silvia Galiano, Silvia Pérez-Silanes, Antonio Monge, Eric Deharo, Ignacio Aldana. "New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities". Bioorg. & Med. Chem. Lett. 2011, 21: 4498-4502.
Science Direct- Bioorganic & Medicinal Chemistry Letters

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Adela Mendoza, Silvia Pérez-Silanes, Miguel Quiliano, Adriana Pabón, Silvia Galiano, Germán González, Giovanny Garavito, Mirko Zimic, Abraham Baisberg, Ignacio Aldana, Antonio Monge, Eric Deharo. "Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships". Exp. Parasitol. 2011, 128: 97-103.  
Science Direct-Experimental Parasitology

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Silvia Pérez-Silanes, Luis Berrade, Rony N. García-Sánchez, Adela Mendoza, Silvia Galiano, Berta Martín-Solórzano, Juan J. Nogal-Ruiz, Antonio R. Martínez-Fernández, Ignacio Aldana, Antonio Monge. "New 1-Aryl-3-Substituted Propanol Derivatives as Antimalarial Agents".
Molecules 2009, 14: 4120-4135.

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Marín, A.; Lima, L. M.; Solano, B.; Vicente, E.; Silanes, S. P.; Maurel, S.; Sauvain, M.; Aldana, I.; Monge, A.; Deharo, E. " Antiplasmodial structure-activity relationship of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide derivatives". Exp. Parasitol. 2008, 118, 25-31.
Science Direct- Experimental Parasitology

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Esther Vicente,  Sarah Charnaud, Emily Bongard, Raquel Villar, Asunción Burguete, Beatriz Solano, Saioa Ancizu, Silvia Pérez-Silanes, Ignacio Aldana, Livia Vivas, Antonio Monge. "Synthesis and Antiplasmodial Activity of 3-Furyl and 3-Thienylquinoxaline-2-carbonitrile 1,4-Di-N-oxide Derivatives".
Molecules 2008, 13, 69-77.

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Esther Vicente, Lidia M. Lima, Emily Bongard, Sarah Charnaud, Raquel Villar, Beatriz Solano, Asunción Burguete, Silvia Perez-Silanes, Ignacio Aldana, Livia Vivas, Antonio Monge. "Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents". Eur. J. Med. Chem. 2008, 43, 1903-1910.
Science Direct-European Journal of Medicinal Chemistry

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Belén Zarranz, Andrés Jaso, Lidia Moreira, Ignacio Aldana, Antonio Monge, Séverine Maurel,Michel Sauvain. "Antiplasmodial activity of 3-trifluoromethyl-2-carbonylquinoxaline di-N-oxide derivatives". Braz. J. Pharm. Sci. 2006, 42, 357-361.

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Zarranz, B.; Jaso, A.; Aldana, I.; Monge, A.; Maurel, S.; Deharo, E.; Jullian, V.; Sauvain, M. "Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives. Arzneimittel Forsch. 2005, 55, 754-761.
Thieme Connect- Arzneimittel Forschung Drug Research

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Aldana, I.; Ortega, M. A.; Jaso, A.; Zarranz, B.; Oporto, P.; Gimenez, A.; Monge, A.; Deharo, E. "Antimalarial activity of some 7-chloro-2-quinoxalinecarbonitrile-1,4,-di-N-oxide derivatives". Pharmazie 2003, 58, 68-69.
Ingenta Connect-Pharmazie

COLABORATIONS

International collaborations of the Malaria Medical chemistry Research team

1. Dr. Adriana Pabón. Grupo de Malaria. Universidad de Antioquía, Medellín (Colombia) (Dr. Adriana Pabón. Malaria Group. Antioquia University, Medellin (Colombia)

2.  Dr. Eric Deharo. Institut de Recherche pour le Développement-Université Paul Sabatier PharmaDEV. Faculté des Sciences Pharmaceutiques. Toulouse (France)

3.  Dr. Giovan Garavito. Universidad Nacional de Colombia. Bogotá (Colombia). (Dr. Giovan Garavito. National University of Colombia. Bogota (Colombia)).

4.  Dr. Mirko Zimic. Universidad Cayetano Heredia. Lima (Perú). (Dr. Mirko Zimic. Cayetano Heredia University. Lima (Perú))

5.  Dr. Julio Caballero. Universidad de Talca. Chile (Dr. Julio Caballero. Talca University. Chile)