1. Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity
- Author
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Ai-Qin Jiang, Zhi-Jun Liu, Hai-Liang Zhu, Yong-Hua Yang, Liang-Qiang He, Yin Luo, and Shuai Zhang
- Subjects
Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Biochemistry ,Flow cytometry ,Focal adhesion ,chemistry.chemical_compound ,Structure-Activity Relationship ,Neoplasms ,Drug Discovery ,medicine ,Moiety ,Humans ,Molecular Biology ,Protein Kinase Inhibitors ,Oxadiazoles ,Benzotriazole ,biology ,medicine.diagnostic_test ,Chemistry ,Organic Chemistry ,Active site ,Triazoles ,Molecular Docking Simulation ,Docking (molecular) ,Apoptosis ,Focal Adhesion Protein-Tyrosine Kinases ,Cancer cell ,biology.protein ,MCF-7 Cells ,Molecular Medicine ,HT29 Cells - 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.
- Published
- 2013