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

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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.

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Acknowledgments

Financial supports of this project by AJA University of Medical Sciences are acknowledged. We gratefully acknowledge the financial support of the Shiraz University of Medical Sciences, vice-chancellor of research.

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Authors and Affiliations

  1. Department of Toxicology, AJA University of Medical Science, PO Box 1411-718541, Tehran, Iran

    Ali Reza Nikkhoo, Nahid Arianpour & Amir Ahmad Salarian

  2. Medicinal & Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, PO Box 3288-71345, Shiraz, Iran

    Ali Reza Nikkhoo, Ramin Miri, Omidreza Firuzi & Ahmad Ebadi

  3. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, PO Box 1583-71345, Shiraz, Iran

    Ali Reza Nikkhoo, Ramin Miri & Ahmad Ebadi

Authors
  1. Ali Reza Nikkhoo
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  2. Ramin Miri
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  3. Nahid Arianpour
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  4. Omidreza Firuzi
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  5. Ahmad Ebadi
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  6. Amir Ahmad Salarian
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Correspondence to Amir Ahmad Salarian.

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Nikkhoo, A.R., Miri, R., Arianpour, N. et al. Cytotoxic activity assessment and c-Src tyrosine kinase docking simulation of thieno[2,3-b] pyridine-based derivatives. Med Chem Res 23, 1225–1233 (2014). https://doi.org/10.1007/s00044-013-0729-7

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  • DOI: https://doi.org/10.1007/s00044-013-0729-7

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