2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling.

ABSTRACT: Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro

SUBMITTER: Ferreira RAA 

PROVIDER: S-EPMC7932521 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature