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New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives: synthesis, antitumor activity, EGFR tyrosine kinase inhibitory activity and molecular modeling studies

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Abstract

New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were synthesized and characterized by analytical and spectrometrical methods (IR, HRMS, 1H, and 13C NMR). Eleven of the synthesized compounds were selected by the National Cancer Institute, USA to be screened for their antitumor activity at a single dose (10 µM) against a panel of 60 cancer cell lines. Also, the EGFR tyrosine kinase inhibitory activity of compounds 4, 5, 8, and 9 was studied. In the present work, structure-based pharmacophore mapping, molecular docking, protein–ligand interaction, fingerprints, and binding energy calculations were employed in a virtual screening strategy to identify the interaction between the compounds and the active site of EGFR tyrosine kinase.

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Acknowledgments

The authors would like to express their sincere thanks to the staff members of the Department of Health and Human Services, National Cancer Institute (NCI), Bethesda, Maryland, USA for performing the antitumor screening of the newly synthesized compounds. Thanks to Georgia State University, USA for carrying out the spectral and elemental analyses. Thanks also to Reaction Biology Corporation, USA for performing EGFR tyrosine kinase assay.

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Authors and Affiliations

  1. Medicinal Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    Moustafa T. Gabr, Nadia S. El-Gohary, Eman R. El-Bendary & Mohamed M. El-Kerdawy

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  1. Moustafa T. Gabr
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  2. Nadia S. El-Gohary
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  3. Eman R. El-Bendary
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  4. Mohamed M. El-Kerdawy
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Correspondence to Nadia S. El-Gohary.

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Gabr, M.T., El-Gohary, N.S., El-Bendary, E.R. et al. New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives: synthesis, antitumor activity, EGFR tyrosine kinase inhibitory activity and molecular modeling studies. Med Chem Res 24, 860–878 (2015). https://doi.org/10.1007/s00044-014-1114-x

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