2. Academic Validation
  3. Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies

Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies

  • Bioorg Med Chem. 2019 Jan 15;27(2):305-314. doi: 10.1016/j.bmc.2018.12.003.
Ehsan Faghih-Mirzaei 1,  Salehe Sabouri 2,  Leila Zeidabadinejad 3,  Salman AbdolahRamazani 4,  Mehdi Abaszadeh 5,  Arash Khodadadi 6,  Mohadeseh Shamsadinipour 6,  Mandana Jafari 7,  Somayeh Pirhadi 8
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
  • 2 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Herbal and Traditional Medicine Research Center, Kerman University of Medical Sciences, Kerman, Iran.
  • 3 Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.
  • 4 Medicinal Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 5 Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 76175493, Iran. Electronic address: abaszadeh@kmu.ac.ir.
  • 6 Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 76175493, Iran.
  • 7 Herbal and Traditional Medicine Research Center, Kerman University of Medical Sciences, Kerman, Iran.
  • 8 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: s_pirhadi@sums.ac.ir.
PMID: 30554970 DOI: 10.1016/j.bmc.2018.12.003
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.

Keywords

Apoptosis; Cancer; Docking; MTT; Metronidazole; Molecular dynamics simulation; QSAR; Synthesis.

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