PUBLICATION
Targeting chalcone binding sites in living Leishmania using a reversible fluorogenic benzochalcone probe
- Authors
- Batista, A.S., Oliveira, S.D.S., Pomel, S., Commere, P.H., Mazan, V., Lee, M., Loiseau, P.M., Rossi-Bergmann, B., Prina, E., Duval, R.
- ID
- ZDB-PUB-220318-13
- Date
- 2022
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 149: 112784 (Journal)
- Registered Authors
- Loiseau, Philippe
- Keywords
- Cell imaging, Chalcones, Cytometry, Fluorescence, Leishmania amazonensis, Pharmacology
- MeSH Terms
-
- Animals
- Antiprotozoal Agents*/chemistry
- Antiprotozoal Agents*/pharmacology
- Binding Sites
- Chalcone*/pharmacology
- Chalcones*/chemistry
- Chalcones*/pharmacology
- Fluorescent Dyes
- Leishmania*
- Zebrafish
- PubMed
- 35299122 Full text @ Biomed. Pharmacother.
Citation
Batista, A.S., Oliveira, S.D.S., Pomel, S., Commere, P.H., Mazan, V., Lee, M., Loiseau, P.M., Rossi-Bergmann, B., Prina, E., Duval, R. (2022) Targeting chalcone binding sites in living Leishmania using a reversible fluorogenic benzochalcone probe. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 149:112784.
Abstract
Chalcones (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. We demonstrate herein that our previously described benzochalcone fluorogenic probe (HAB) could be imaged by fluorescence microscopy in live Leishmania amazonensis promastigotes where it targeted the parasite acidocalcisomes, lysosomes and the mitochondrion. As in the live zebrafish model, HAB formed yellow-emitting fluorescent complexes when associated with biological targets in Leishmania. Further, 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. This pharmacological evaluation suggested that the binding of HAB in promastigotes was representative of chalcone pharmacology in Leishmania, 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. However, 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. This advocates for further optimization of this undirect target detection strategy using pharmacophore-derived reversible fluorescent probes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping