Original Research

Medicinal Chemistry Research

, Volume 23, Issue 3, pp 1225-1233

Cytotoxic activity assessment and c-Src tyrosine kinase docking simulation of thieno[2,3-b] pyridine-based derivatives

  • Ali Reza NikkhooAffiliated withDepartment of Toxicology, AJA University of Medical ScienceMedicinal & Natural Products Chemistry Research Center, Shiraz University of Medical SciencesDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences
  • , Ramin MiriAffiliated withMedicinal & Natural Products Chemistry Research Center, Shiraz University of Medical SciencesDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences
  • , Nahid ArianpourAffiliated withDepartment of Toxicology, AJA University of Medical Science
  • , Omidreza FiruziAffiliated withMedicinal & Natural Products Chemistry Research Center, Shiraz University of Medical Sciences
  • , Ahmad EbadiAffiliated withMedicinal & Natural Products Chemistry Research Center, Shiraz University of Medical SciencesDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences
  • , Amir Ahmad SalarianAffiliated withDepartment of Toxicology, AJA University of Medical Science Email author 

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Abstract

Thienopyridine derivatives possess various promising biological properties and particularly cytotoxic effect. In vitro cytotoxic activities of some thienopyridine analogous were evaluated by MTT reduction assay in three human cancer cell lines (HL-60, MCF-7, and LS-180). The compounds showed a wide range of cytotoxic activities and their IC50 values ranged from 0.2 to 100 μM and above. Compound 4e was the most potent derivative and 4i showed good cytotoxic activity against all three cell lines (IC50 <20 μM). Docking simulation of thienopyridine derivatives was implemented on c-Src tyrosine kinase involved in tumor progression and metastases. Results showed that these compounds might potentially bind to the key amino acid Thr339 in the c-Src tyrosine kinase active site. Ligand efficiency (LE) values calculated by using free binding energies obtained from experimental data were predicted by the docking study. Also, experimental and predicted LEs were in good agreement. Based on the LE indices and other findings, some of the thienopyridine derivatives might be efficient candidates for further development as anticancer agents.

Keywords

Thienopyridine Cytotoxic activity Docking simulation Ligand efficiency