Synthesis of 4-(2-Phenylhydrazono)-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-one Compounds and Characterization of Their Affinities to Anti-apoptotic Bcl-2 Family Proteins

Authors

  • Shicheng Shi,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Li Han,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Mi Zhou,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Yangfeng Li,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Zhen Liu,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Biao Yu,

    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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  • Renxiao Wang

    Corresponding author
    1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
    • State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China, Tel.: 0086-021-54925128
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Abstract

Organic compounds containing the thiazol-2-yl-1H-pyrazol-5(4H)-one moiety are known to be associated with versatile pharmacological applications. In this study, we describe the methods for preparing 4-(2-phenylhydrazono)-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-one compounds. A set of 26 compounds were synthesized with overall yields ranging between 37% –92%. They were tested in a fluorescence polarization-based binding assay against three anti-apoptotic Bcl-2 family proteins, including Bcl-xL, Bcl-2, and Mcl-1. Our results indicate that this class of compounds are not effective inhibitors of these anti-apoptotic Bcl-2 family proteins. Their apoptosis-inducing effects are possibly due to BAX activation as suggested by Gavathiotis et al. in their recent study. However, other possibilities should not be ignored. In addition, a crystal structure obtained by us reveals that the exocyclic double bond in the molecular structure of this class of compounds is in the (Z)-configuration

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