Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases.
J Med Chem
; 67(2): 1460-1480, 2024 Jan 25.
Article
in En
| MEDLINE
| ID: mdl-38214254
ABSTRACT
While progress has been made in the effort to eradicate malaria, the disease remains a significant threat to global health. Acquired resistance to frontline treatments is emerging in Africa, urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound 1 as a lead antimalarial, which was initially developed to target human ephrin type A receptor 2 (EphA2). Here, we report a structure-activity relationship study and lead optimization of compound 1, which led to compound 33, with improved antimalarial activity and selectivity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor, EphA2
/
Malaria
/
Antimalarials
Limits:
Humans
Country/Region as subject:
Africa
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
United States