Synthesis, biological activities, and docking studies of d-pantolactone derivatives as novel FAS inhibitors.
Bioorg Med Chem
; 27(20): 115069, 2019 10 15.
Article
em En
| MEDLINE
| ID: mdl-31492533
ABSTRACT
A novel series of fatty acid synthase (FAS) inhibitors with D-(-)-pantolactone moiety and potential utility for the treatment of obesity were designed, synthesized and characterized, in which the structure of compound 3k was further confirmed by single X-ray diffraction. The mouse FAS inhibitory activity of synthesized compounds was evaluated. Major synthesized compounds (except 3g, 3i, 3k, 3l, and 3n) exhibited moderate FAS inhibitory properties with IC50 values in the range of 13.68⯱â¯1.52-33.19⯱â¯1.39⯵M, reference inhibitor C75 has IC50 value of 13.86⯱â¯2.79⯵M. Eight compounds (3c, 3d, 3e, 3f, 3j, 3m, 3q and 3r) also displayed inhibitory effect on lipid accumulation in human HepG2 cells. Additionally, the molecular docking study revealed that compound 3m having good inhibition activity against FAS and lipid accumulation also showed promising binding affinities with hFAS, while its binding model with hFAS (PDB ID 4PIV) was different from that of reference compound C75.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
4-Butirolactona
/
Receptor fas
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Inibidores Enzimáticos
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Simulação de Acoplamento Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article