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

Organic compounds containing the thiazol-2-yl-lH-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）- l-（4-phenylthiazol-2-yl）-1H-pyrazol-5（4H）-one compounds. A set of 26 compounds...

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Bibliographic Details
Published in中国化学：英文版 no. 9; pp. 1133 - 1138
Main Author Shicheng Shi Li Han Mi Zhou Yangfeng Li Zhen Li Biao Yu Renxiao Wang
Format Journal Article
LanguageEnglish
Published 2013
Subjects
Bcl-2家族蛋白
合成
吡唑
噻唑
抗凋亡
有机化合物
肼基
苯基
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Summary:Organic compounds containing the thiazol-2-yl-lH-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）- l-（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 ef- fects 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.
Bibliography:Organic compounds containing the thiazol-2-yl-lH-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）- l-（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 ef- fects 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.
31-1547/O6
apoptosis inducer, BAX activation, Bcl-2 inhibition, protein-protein interaction, small-molecule in-hibitor
ISSN:1001-604X
1614-7065