A Library of Thiazolidin-4-one Derivatives as Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors: An Attempt To Discover Novel Antidiabetic Agents.
ChemMedChem
; 15(13): 1229-1242, 2020 07 03.
Article
em En
| MEDLINE
| ID: mdl-32390300
ABSTRACT
Protein tyrosine phosphatase 1B (PTP1B) is an important target for the treatment of diabetes. A series of thiazolidin-4-one derivatives 8-22 was designed, synthesized and investigated as PTP1B inhibitors. The new molecules inhibited PTP1B with IC50 values in the micromolar range. 5-(Furan-2-ylmethylene)-2-(4-nitrophenylimino)thiazolidin-4-one (17) exhibited potency with a competitive type of enzyme inhibition. structure-activity relationship studies revealed various structural facets important for the potency of these analogues. The findings revealed a requirement for a nitro group-including hydrophobic heteroaryl ring for PTP1B inhibition. Molecular docking studies afforded good correlation with experimental results. H-bonding and π-π interactions were responsible for optimal binding and effective stabilization of virtual protein-ligand complexes. Furthermore, in-silico pharmacokinetic properties of test compounds predicted their drug-like characteristics for potential oral use as antidiabetic agents.Additionally, a binding site model demonstrating crucial pharmacophoric characteristics influencing potency and binding affinity of inhibitors has been proposed, which can be employed in the design of future potential PTP1B inhibitors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores Enzimáticos
/
Tiazolidinas
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Proteína Tirosina Fosfatase não Receptora Tipo 1
/
Descoberta de Drogas
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Hipoglicemiantes
/
Antiprotozoários
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Índia