1443986-16-0Relevant articles and documents
A small-molecule cell-based screen led to the identification of biphenylimidazoazines with highly potent and broad-spectrum anti-apicomplexan activity
Moine, Espérance,Denevault-Sabourin, Caroline,Debierre-Grockiego, Fran?oise,Silpa, Laurence,Gorgette, Olivier,Barale, Jean-Christophe,Jacquiet, Philippe,Brossier, Fabien,Gueiffier, Alain,Dimier-Poisson, Isabelle,Enguehard-Gueiffier, Cécile
, p. 386 - 400 (2014/12/11)
An in vitro screening of the anti-apicomplexan activity of 51 compounds, stemming from our chemical library and from chemical synthesis, was performed. As a study model, we used Toxoplasma gondii (T. gondii), expressing β-galactosidase for the colorimetric assessment of drug activity on parasites cultivated in vitro. This approach allowed the validation of a new series of molecules with a biphenylimidazoazine scaffold as inhibitors of T. gondii growth in vitro. Hence, 8 molecules significantly inhibited intracellular replication of T. gondii in vitro, with EC50 50 in the submicromolar to nanomolar range, for each parasite. These data, including the broad anti-parasite spectrum of these inhibitors, define a new generation of potential anti-parasite compounds of wide interest, including for veterinary application. Studies realized on E. tenella suggest that these molecules act during the intracellular development steps of the parasite. Further experiments should be done to identify the molecular target(s) of these compounds.
