Correlation Engine 2.0
Clear Search sequence regions


  • acid (1)
  • alamar blue (1)
  • american trypanosomiasis (2)
  • amino acids (3)
  • behavior (2)
  • benznidazol (1)
  • blood (7)
  • brain (1)
  • brazil (1)
  • bromide (1)
  • carbon (2)
  • cases (2)
  • catalysis (1)
  • cells t (1)
  • chagas disease (6)
  • chronic disease (1)
  • compound benzyl (1)
  • control parasites (1)
  • crystal (2)
  • dimers (1)
  • direct (1)
  • disadvantages (1)
  • dmso (7)
  • dye (1)
  • edta (2)
  • el salvador (1)
  • entamoeba histolytica (1)
  • essential (4)
  • ester (4)
  • feces (1)
  • format (1)
  • formazan (2)
  • furan (1)
  • heart (1)
  • heat (1)
  • hepes (1)
  • host cell (1)
  • humans (3)
  • hydrogen bonds (1)
  • hydrogens (1)
  • k2hpo4 (1)
  • latin america (1)
  • least squares (1)
  • leishmania (1)
  • life cycle (4)
  • ligand (5)
  • liver (1)
  • lysis (8)
  • m 8 (3)
  • macrophage (3)
  • mammal (2)
  • methyl (17)
  • mexico (5)
  • mice (2)
  • molecular weights (3)
  • mtt (2)
  • mycobacterium tuberculosis (1)
  • nadph (3)
  • nifurtimox (5)
  • nitrogen (1)
  • oxide (69)
  • oxygen (2)
  • parasites (3)
  • patient (2)
  • period (2)
  • phase (8)
  • plasmodium falciparum (1)
  • protein t (1)
  • protozoa (2)
  • public health (1)
  • quinoxalines (1)
  • rcsb (1)
  • receptor (1)
  • research (2)
  • RPMI (1)
  • salts (1)
  • serum (3)
  • slide (1)
  • sodium heparin (1)
  • spp 15 (1)
  • spp 17 (1)
  • sulfur (1)
  • t 107 (1)
  • t 108 (2)
  • taiwan (1)
  • toxic (1)
  • TR (27)
  • trichomonas (1)
  • trypan blue (1)
  • trypanosoma cruzi (1)
  • TS2 (4)
  • Sizes of these terms reflect their relevance to your search.

    Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.

    Citation

    Karla Fabiola Chacón-Vargas, Benjamin Nogueda-Torres, Luvia E Sánchez-Torres, Erick Suarez-Contreras, Juan Carlos Villalobos-Rocha, Yuridia Torres-Martinez, Edgar E Lara-Ramirez, Giulia Fiorani, R Luise Krauth-Siegel, Maria Laura Bolognesi, Antonio Monge, Gildardo Rivera. Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors. Molecules (Basel, Switzerland). 2017 Feb 01;22(2)

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 28157150

    View Full Text