1. Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies
- Author
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Mehdi Abaszadeh, Salman AbdolahRamazani, Mohadeseh Shamsadinipour, Arash Khodadadi, Mandana Jafari, Somayeh Pirhadi, Salehe Sabouri, Ehsan Faghih-Mirzaei, and Leila Zeidabadinejad
- Subjects
Quantitative structure–activity relationship ,Clinical Biochemistry ,Protein Data Bank (RCSB PDB) ,Quantitative Structure-Activity Relationship ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Molecular Dynamics Simulation ,01 natural sciences ,Biochemistry ,Flow cytometry ,Catalytic Domain ,Cell Line, Tumor ,Metronidazole ,Drug Discovery ,medicine ,Humans ,Cytotoxic T cell ,MTT assay ,Protein Kinase Inhibitors ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Molecular Structure ,medicine.diagnostic_test ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Docking (molecular) ,Focal Adhesion Kinase 1 ,Molecular Medicine ,Azole ,Target protein ,Drug Screening Assays, Antitumor ,Protein Binding - Abstract
A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM ), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK. more...
- Published
- 2019
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