@article{fdi:010086851,
  title = {{T}argeting chalcone binding sites in living {L}eishmania using a reversible fluorogenic benzochalcone probe},
  author = {{B}atista, {A}. {S}. and {O}liveira, {S}. {D}. {S}. and {P}omel, {S}. and {C}ommere, {P}. {H}. and {M}azan, {V}. and {L}ee, {M}. and {L}oiseau, {P}. {M}. and {R}ossi-{B}ergmann, {B}. and {P}rina, {E}. and {D}uval, {R}omain},
  editor = {},
  language = {{ENG}},
  abstract = {{C}halcones (1,3-diphenyl-2-propen-1-ones) either natural or synthetic have a plethora of biological properties including antileishmanial activities, but their development as drugs is hampered by their largely unknown mechanisms of action. {W}e demonstrate herein that our previously described benzochalcone fluorogenic probe ({HAB}) could be imaged by fluorescence microscopy in live {L}eishmania amazonensis promastigotes where it targeted the parasite acidocalcisomes, lysosomes and the mitochondrion. {A}s in the live zebrafish model, {HAB} formed yellow-emitting fluorescent complexes when associated with biological targets in {L}eishmania. {F}urther, we used {HAB} as a reversible probe to study the binding of a portfolio of diverse chalcones and analogues in live promastigotes, using a combination of competitive flow cytometry analysis and cell microscopy. {T}his pharmacological evaluation suggested that the binding of {HAB} in promastigotes was representative of chalcone pharmacology in {L}eishmania, with certain exogenous chalcones exhibiting competitive inhibition (ca. 20-30%) towards {HAB} whereas non-chalconic inhibitors showed weak capacity (ca. 3-5%) to block the probe intracellular binding. {H}owever, this methodology was restricted by the strong toxicity of several competing chalcones at high concentration, in conjunction with the limited sensitivity of the {HAB} fluorophore. {T}his advocates for further optimization of this undirect target detection strategy using pharmacophore-derived reversible fluorescent probes.},
  keywords = {{C}halcones ; {L}eishmania amazonensis ; {F}luorescence ; {C}ell imaging ; {C}ytometry ; {P}harmacology},
  booktitle = {},
  journal = {{B}iomedicine and {P}harmacotherapy},
  volume = {149},
  numero = {},
  pages = {12784 [9 ]},
  ISSN = {0753-3322},
  year = {2022},
  DOI = {10.1016/j.biopha.2022.112784},
  URL = {https://www.documentation.ird.fr/hor/fdi:010086851},
}