title: Evaluation of the Novel Antichagasic Activity of [1,2,3]Triazolo[1,5-a]pyridine Derivatives.
abstract: BACKGROUND
  Trypanosoma cruzi is the causative agent of Chagas disease. This parasite is vulnerable to the effects of ROS as its main defense mechanism against exogenous agents trypanothione is also another weakness of the parasite that investigated related to the inhibition of enzymes belonging P450 system, mainly CYP51. In our group we have synthesized a series of triazoles known as [1,2,3]triazolo[1,5-a]pyridyl ketones, and pyridyl ketones. These families have shown interesting structural features due to the presence of electron withdrawing moieties attached to the main heterocycle (triazoles and/or pyridines) and are proposed as potential target in the parasite, by the presence of the carbonyl group being able to be reduced and form a free radical that could interact with molecular oxygen generating ROS in the parasite. Furthermore, the triazole ring and pyridines have been considered as potent inhibitors of sterol biosynthesis, the lock being part CYP51.
  
  
  RESULTS
  Our results showed that the series is capable of generating a stable radical species and generate ROS in the parasite. On the other hand these molecules are potent inhibitors of enzymes belonging to the complex P450. We have focused on the inhibition of ergosterol biosynthesis demonstrating that triazole/ pyridine families are able to affect this pathway being observed the accumulation of squalene and lanosterol.
authors: Michel
authors: M
authors: Lapier
authors: Maria C
authors: MC
authors: Zuniga-Lopez
authors: Benjamin
authors: B
authors: Aguilera-Venegas
authors: Rosa
authors: R
authors: Adam
authors: Belen
authors: B
authors: Abarca
authors: Rafael
authors: R
authors: Ballesteros
authors: Rodrigo
authors: R
authors: Lopez-Munoz
authors: Juan Diego
authors: JD
authors: Maya
authors: Department of Inorganic and Analytical, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Santiago, Chile, Casilla 233, Santiago, Chile.
authors: Claudio
authors: C
authors: Olea-Azar
mesh_terms: D049109:Cell Proliferation; D014355:Chagas Disease / Q000188:drug therapy*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D013058:Mass Spectrometry; D011725:Pyridines / Q000737:chemistry / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D011725:Pyridines; D014344:Trypanocidal Agents