@article{fdi:010078998,
  title = {{N}ew 8-{N}itroquinolinone derivative displaying submicromolar in vitro activities against both {T}rypanosoma brucei and cruzi},
  author = {{P}edron, {J}. and {B}oudot, {C}. and {B}rossas, {J}. {Y}. and {P}inault, {E}. and {B}ourgeade-{D}elmas, {S}andra and {S}ournia-{S}aquet, {A}. and {B}outet-{R}obinet, {E}. and {D}estere, {A}. and {T}ronnet, {A}. and {B}erge, {J}. and {B}onduelle, {C}. and {D}eraeve, {C}. and {P}ratviel, {G}. and {S}tigliani, {J}. {L}. and {P}aris, {L}. and {M}azier, {D}. and {C}orvaisier, {S}. and {S}ince, {M}. and {M}alzert-{F}reon, {A}. and {W}yllie, {S}. and {M}ilne, {R}. and {F}airlamb, {A}. {H}. and {V}alentin, {A}. and {C}ourtioux, {B}. and {V}erhaeghe, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {nitroquinolin-2(1{H})-one pharmacophore. {F}ifteen new derivatives were synthesized and evaluated in vitro against {L}. infantum, {T}. brucei brucei, and {T}. cruzi, in parallel with a cytotoxicity assay on the human {H}ep{G}2 cell line. {A} potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting {EC}50 values of 12 and 500 n{M} on {T}. b. brucei trypomastigotes and {T}. cruzi amastigotes respectively, in comparison with four reference drugs (30 n{M} <= {EC}50 <= 13 mu {M}). {M}oreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. {F}inally, molecule 12 ({E} degrees = -0.37 {V}/{NHE}) was shown to be bioactivated by type 1 nitroreductases, in both {L}eishmania and {T}rypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds.},
  keywords = {{T}rypanosoma brucei brucei ; {T}rypanosoma cruzi ; 8-nitroquinolin-2(1{H})-ones ; redox potentials ; {NTR}1},
  booktitle = {},
  journal = {{ACS} {M}edicinal {C}hemistry {L}etters},
  volume = {11},
  numero = {4},
  pages = {464--472},
  ISSN = {1948-5875},
  year = {2020},
  DOI = {10.1021/acsmedchemlett.9b00566},
  URL = {https://www.documentation.ird.fr/hor/fdi:010078998},
}