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The uses of cyclohexan-1,4-dione for the synthesis of thiophene derivatives as new anti-proliferative, prostate anticancer, c-Met and tyrosine kinase inhibitors

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Abstract

A series of heterocyclic compounds derived from the dihydrobenzo[b]thiophene derivatives were synthesized all the synthesized compounds were determined by elemental analysis, 1H NMR, 13C NMR, and MS. The newly synthesized compounds were evaluated for their in-vitro cytotoxic activity against c-Met kinase, and the six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721). All target compounds were initially tested for their anti-proliferative activity against human prostatic cancer PC-3 cell line. The most promising compounds were 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 7b, 7c, 11c, 11d, and 11f were further investigated against tyrosin kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 5e, 5f, 5h, 11d, and 11f were selected to examine their Pim-1 kinase inhibition activity where compounds 5e, 5h, and 11f showed high activities.

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Acknowledgements

R. M. Mohareb would like to thank the Alexander von Humboldt Foundation in Bonn, Germany for affording him regular fellowship for doing research and completing this work.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science Cairo University, New Cairo, AR, Egypt

    Rafat M. Mohareb

  2. Department of Chemistry, Faculty of Science, Kuwait University, P.O. box 12613, Safat, 13060, Kuwait

    Fatima Al-Omran

  3. Institute of Engineering and Technology, El-Tagammoe El-Khames, New Cairo, AR, Egypt

    Rehab A. Ibrahim

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  1. Rafat M. Mohareb
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  2. Fatima Al-Omran
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Correspondence to Rafat M. Mohareb.

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Mohareb, R.M., Al-Omran, F. & Ibrahim, R.A. The uses of cyclohexan-1,4-dione for the synthesis of thiophene derivatives as new anti-proliferative, prostate anticancer, c-Met and tyrosine kinase inhibitors. Med Chem Res 27, 618–633 (2018). https://doi.org/10.1007/s00044-017-2087-3

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  • DOI: https://doi.org/10.1007/s00044-017-2087-3

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