Corrigendum: Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

[This corrects the article DOI: 10.3389/fmicb.2023.

Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

species, , and are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.

Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity.

Human African trypanosomiasis is a neglected tropical disease (NTD) that is fatal if left untreated. Although approximately 13 million people live in moderate- to high-risk areas for infection, current treatments are plagued by problems with safety, efficacy, and emerging resistance. In an effort to fill the drug development pipeline for HAT, we have expanded previous work exploring the chemotype represented by the compound , with a particular focus on improvement of absorption, distribution, metabolism and elimination (ADME) properties.

Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-]pyridazines for the Treatment of Human African Trypanosomiasis.

From a high-throughput screen of 42 444 known human kinases inhibitors, a pyrazolo[1,5-]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against human kinases GSK-3β, CDK-2, and CDK-4 were leveraged to try to improve the selectivity of the series, resulting in which showed selectivity for over these three human enzymes. In parallel, properties known to influence the absorption, distribution, metabolism, and excretion (ADME) profile of the series were optimized resulting in being progressed into an efficacy study in mice.