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

Authors :: Saccoliti F
Madia VN
Tudino V
De Leo A
Pescatori L
Messore A
De Vita D
Scipione L
Brun R
Kaiser M
Mäser P
Calvet CM
Jennings GK
Podust LM
Costi R
Di Santo R
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2018 Aug 05; Vol. 156, pp. 53-60. Date of Electronic Publication: 2018 Jun 28.
Publication Year :: 2018
Abstract: 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 IC <subscript>50</subscript> 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.<br /> (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

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