Discovery of 4-((1-(1H-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of Trypanosoma cruzi growth inhibitors.

Discovery of 4-((1-(1H-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of Trypanosoma cruzi growth inhibitors.
Bioorg Med Chem Lett. 2020 Feb 22;:127052
Authors: Ponzi S, Bresciani A, Kaiser M, Nardi V, Nizi E, Ontoria JM, Pace P, Paonessa G, Summa V, Harper S
Abstract
The identification of a new series of growth inhibitors of Trypanosoma cruzi, the causative agent of Chagas' disease, is described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC50 ≤ 100 nM) and no cytotoxicity in human cells (HeLa CC50 > 50 μM). Further investigation identified CYP51 inhibition (compound 11 CYP51 IC50 52 nM) as a possible mechanism of action of this new class of anti-parasitic agents.
PMID: 32113841 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - February 21, 2020 Category: Chemistry Authors: Ponzi S, Bresciani A, Kaiser M, Nardi V, Nizi E, Ontoria JM, Pace P, Paonessa G, Summa V, Harper S Tags: Bioorg Med Chem Lett Source Type: research