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Bioorg Med Chem Lett. 2020 Jan 1;30(1):126778. doi: 10.1016/j.bmcl.2019.126778. Epub 2019 Oct 31.

A new chemotype with promise against Trypanosoma cruzi.

Author information

1
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, United States.
2
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH-4003 Basel, Switzerland.
3
Department of Medicine, University of Washington, 750 Republican Street, Seattle, WA, United States.
4
Department of Biochemistry, Vanderbilt University, 2200 Pierce Ave., Nashville, TN, United States.
5
Department of Biology, University of Nebraska at Omaha, Omaha, NE, United States.
6
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, United States. Electronic address: jvenners@unmc.edu.

Abstract

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure-activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

KEYWORDS:

Chagas disease; SAR; Trypanosoma cruzi

PMID:
31706668
PMCID:
PMC6892603
[Available on 2021-01-01]
DOI:
10.1016/j.bmcl.2019.126778

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