Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity.
Bioorg Med Chem
; 21(13): 3723-9, 2013 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-23673215
ABSTRACT
1,3,4-Oxadiazole derivatives have drawn continuing interest over the years because of their varied biological activities. In order to search for novel anticancer agents, we designed and synthesized a series of new 1,3,4-oxadiazole derivatives containing benzotriazole moiety as potential focal adhesion kinase (FAK) inhibitors. All the synthesized compounds were firstly reported. Among the compounds, compound 4 shows the most potent inhibitory activity against MCF-7 and HT29 cell lines with IC50 values of 5.68 µg/ml and 10.21 µg/ml, respectively. Besides, all the compounds were assayed for FAK inhibitory activity using the TRAP-PCR-ELISA assay. The results showed compound 4 exhibited the most potent FAK inhibitory activity with IC50 values of 1.2±0.3 µM. Docking simulation by positioning compound 4 into the FAK structure active site was performed to explore the possible binding mode. Apoptosis which was analyzed by flow cytometry, demonstrated that compound 4 induced apoptosis against MCF-7 cells. Therefore, compound 4 may be a potential anticancer agent against MCF-7 cancer cell.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxidiazóis
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Triazóis
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Proteína-Tirosina Quinases de Adesão Focal
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article