Supramolecular chemistry
Supramolecular Chemistry in antiparasitic drug design
Personnel
Dr Pilar Navarro
Due to the interdisciplinary nature of this project, it is being done in collaboration with different research groups.
Collaborations
• Prof. F. Gómez-Contreras, Departamento de Química Orgánica, Facultad de Química, Universidad Complutense de Madrid (UCM), Spain
• Prof. E. García-España, Departamento de Química Inorgánica, Instituto de Ciencia Molecular, Universidad de Valencia, Spain
• Prof. M. Sanchez-Moreno, Departamento de Parasitologia, Facultad de Ciencias, Granada, Spain
Research Topic
Search for synthetic receptors of antiparasitic activity which are able to inhibit FeSOD
It has been shown that, in general, parasitic protozoan survival is closely related to the ability of enzymes for evading toxic free radical damage originated by their host.
Trypanosoma cruzi possesses a variety of enzymatic antioxidant defenses. Among them iron superoxide dismutase (FeSOD) appears to be the enzyme normaly associated with trypanosomatides and plays a relevant role. Therefore compounds with the ability of inhibiting the protective action of FeSOD are good targets for antiparasitic activity affecting both the growth and survival of parasitic cells. Due to the predominant role of the prostetic groups, competitive complexation of the metal ion of FeSOD could be an efficient way of deactivating the antioxidant effect of the enzyme. We have found a series of 1,4-bis(amino)- and 1-amino-4-chlorobenzo[g]phthalazine derivatives with complexing ability toward transition metal ions, that behave as FeSOD inhibitors and in which the mode of complexation could be related to the enzyme inhibition patterns and antiparasitical activity observed.
Active Project
“Heterocyclic Supramolecular Chemistry. Supported receptors for the recognition of substances of biological or/and environmental interest”
Proyect CTQ2009-14288-C04-01
Finantial support : MCINN
Found: 268.620 euros
From 1-1-2010 until 31-12-2012
Principal Investigator: Enrique García-España
Significant publications
“Efficient inhibition of iron superoxide dismutase and Trypanosoma cruzi growth by benzo[g]phthalazine derivatives funtionalized with one or two imidazole rings”
Sanz, A.M.; Gomez-Contreras, F.*; Navarro, P.; Sanchez-Moreno, M.; Boutaleb-Charki, S.; Campuzano, J.; Pardo, M.; Osuna, A.;Cano, C.; Yunta, M.J.R.; and Campayo, L.
J. Med. Chem. 2008, 51, 1962-1966.
“1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi”.
Rodríguez-Ciria, M.; Sanz, A.M.; Yunta, M.J.R.; Gomez-Contreras, F.*; Navarro, P.; Sanchez-Moreno, M.; Boutaleb-Charki, S.; Osuna, A.; Castiñeiras, A.; Pardo, M.; Cano, C.; Campayo, L.
Bioorg. Med. Chem. 2007, 15, 2081-2091."
