1.
ChemMedChem
; 17(22): e202200418, 2022 11 18.
Artigo
em Inglês
| MEDLINE
| ID: mdl-36193872
RESUMO
A series of 5-[(phenethylamino)methyl]pyrimidine-2,4-diamines were assessed in silico as potential inhibitors of Plasmodium falciparum dihydrofolate reductase (PfDHFR), synthesised and tested for inhibitory activity against PfDHFR inâ vitro. The compounds displayed promising inhibitory activity against both wild-type (Ki 1.3-243â nM) and quadruple mutant (Ki 13-208â nM) PfDHFR in the biochemical enzyme assay, but were less potent in the whole-cell P. falciparum assay (IC50 (TM4/8.2) 0.4-28â µM; IC50 (V1S) 3.7-54â µM). Further investigation into the pharmacokinetic properties of these compounds may guide the development of more potent analogues.