Details

Autor(en) / Beteiligte

• Saccoliti, Francesco
• Madia, Valentina Noemi
• Tudino, Valeria
• De Leo, Alessandro
• Pescatori, Luca
• Messore, Antonella
• De Vita, Daniela
• Scipione, Luigi
• Brun, Reto
• Kaiser, Marcel
• Mäser, Pascal
• Calvet, Claudia Magalhaes
• Jennings, Gareth K.
• Podust, Larissa M.
• Costi, Roberta
• Di Santo, Roberto

Titel

Biological evaluation and structure-activity relationships of imidazole-based compounds as antiprotozoal agents

Ist Teil von

• European journal of medicinal chemistry, 2018-08, Vol.156, p.53-60

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• We discovered a series of azole antifungal compounds as effective antiprotozoal agents. They displayed promising inhibitory activities within the micromolar-submicromolar range against P. falciparum, L. donovani, and T. b. rhodesiense. Moreover, most of such compounds showed excellent nanomolar IC50 against T. cruzi, showing also very low cytotoxicity. Discussion of structure-activity relationships and biological data for these compounds are provided against the different parasites. To assess the mechanism of action against T. cruzi we proved that the most potent compounds (3b, 3j-l) inhibited the T. cruzi CYP51. Moreover, the most active derivative 3j dramatically reduced parasitemia in T. cruzi mouse model without acute toxicity. [Display omitted] •Discovery of in-house antifungal compounds as effective antiprotozoal agents.•Most derivatives showed excellent nanomolar anti-T. cruzi activities.•The most active compounds displayed high selectivity index.•Derivative 3j effectively reduced parasitemia in mice displaying no acute toxicity.