@article{PAR00025096,
  title = {{I}mproving aqueous solubility and in vitro pharmacokinetic properties of the 3-nitroimidazo[1,2-a]pyridine antileishmanial pharmacophore},
  author = {{P}aoli-{L}ombardo, {R}. and {P}rimas, {N}. and {B}ourgeade-{D}elmas, {S}andra and {H}utter, {S}. and {S}ournia-{S}aquet, {A}. and {B}oudot, {C}. and {B}renot, {E}. and {C}astera-{D}ucros, {C}. and {C}orvaisier, {S}. and {S}ince, {M}. and {M}alzert-{F}reon, {A}. and {C}ourtioux, {B}. and {V}alentin, {A}. and {V}erhaeghe, {P}. and {A}zas, {N}. and {R}athelot, {P}. and {V}anelle, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}n antileishmanial structure-activity relationship ({SAR}) study focused on positions 2 and 8 of the imidazo[1,2-a]pyridine ring was conducted through the synthesis of 22 new derivatives. {A}fter being screened on the promatigote and axenic amastigote stages of {L}eishmania donovani and {L}. infantum, the best compounds were tested against the intracellular amastigote stage of {L}. infantum and evaluated regarding their in vitro physicochemical and pharmacokinetic properties, leading to the discovery of a new antileishmanial6-chloro-3-nitro-8-(pyridin-4-yl)-2-[(3,3,3-trifluoropropylsulfonyl)methyl]imidazo[1,2-a]pyridine hit. {I}t displayed low cytotoxicities on both {H}ep{G}2 and {THP}1 cell lines ({CC}50 > 100 mu {M}) associated with a good activity against the intracellular amastigote stage of {L}. infantum ({EC}50 = 3.7 mu {M} versus 0.4 and 15.9 mu {M} for miltefosine and fexinidazole, used as antileishmanial drug references). {M}oreover, in comparison with previously reported derivatives in the studied series, this compound displayed greatly improved aqueous solubility, good mouse microsomal stability ({T}-1/2 > 40 min) and high gastrointestinal permeability in a {PAMPA} model, making it an ideal candidate for further in vivo studies on an infectious mouse model.},
  keywords = {{I}midazo[1,2-a]pyridine ; nitroaromatic ; nitroreductases ; {L}eishmania spp. ; structure-activity relationships ; thermodynamic solubility ; microsomal ; stability ; gastrointestinal permeability},
  booktitle = {},
  journal = {{P}harmaceuticals},
  volume = {15},
  numero = {8},
  pages = {998 [24 p.]},
  year = {2022},
  DOI = {10.3390/ph15080998},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00025096},
}