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Keywords:

  • apoptosis inducer;
  • BAX activation;
  • Bcl-2 inhibition;
  • protein-protein interaction;
  • small-molecule inhibitor

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