Molecules (Apr 2019)

Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets

  • Strahinja Stevanovic,
  • Milan Sencanski,
  • Mathieu Danel,
  • Christophe Menendez,
  • Roumaissa Belguedj,
  • Abdelmalek Bouraiou,
  • Katarina Nikolic,
  • Sandrine Cojean,
  • Philippe M. Loiseau,
  • Sanja Glisic,
  • Michel Baltas,
  • Alfonso T. García-Sosa

DOI
https://doi.org/10.3390/molecules24071282
Journal volume & issue
Vol. 24, no. 7
p. 1282

Abstract

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Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 µM on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.

Keywords