Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX-2

Authors

  • Mohammed I. El-Gamal,

    1. Center for Biomaterials, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
    2. Department of Biomolecular Science, University of Science and Technology, Yuseong-gu, Daejeon, Korea
    3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
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  • Hong Seok Choi,

    1. College of Pharmacy, Chosun University, Gwangju, Korea
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  • Kyung Ho Yoo,

    1. Chemical Kinomics Research Center, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
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  • Daejin Baek,

    1. Department of Chemistry, Hanseo University, Seosan, Korea
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  • Chang-Hyun Oh

    Corresponding author
    1. Center for Biomaterials, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
    2. Department of Biomolecular Science, University of Science and Technology, Yuseong-gu, Daejeon, Korea
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Abstract

A series of 3,4-diarylpyrazole-1-carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single-dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase-2 inhibition and ERK pathway inhibition.

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