Synthesis, dihydrofolate reductase inhibition, anti-proliferative testing, and saturation transfer difference ¹H-NMR study of some new 2-substituted-4,6-diaminopyrimidine derivatives.
Chem Pharm Bull (Tokyo)
; 60(1): 70-8, 2012.
Article
em En
| MEDLINE
| ID: mdl-22223377
ABSTRACT
A series of 2-substituted-4,6-diaminipyrimidine derivatives were synthesized and evaluated for their dihydrofolate reductase (DHFR) inhibitory activity. Saturation transfer difference (STD) (1)H-NMR experiments were used to probe the binding characteristics of the compounds with human DHFR enzyme. The most potent molecules, 12 and 15, in enzyme assay study showed the best results in STD experiments indicating their intimate interaction with the receptor. The docking studies were followed to explain the structural basis for the observed interaction between the ligands and DHFR. All the compounds were also assayed in vitro for their growth inhibitory activity on MCF-7, HepG2, SKHep1, and Hela tumor cell lines. Compounds 16, 17, and 22 demonstrated the most potent in vitro anti-proliferative activity among the others.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Tetra-Hidrofolato Desidrogenase
/
Inibidores Enzimáticos
/
Antagonistas do Ácido Fólico
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article