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

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 This class of compounds are not effective binders of anti‐apoptotic Bcl‐2 family proteins. Their apoptosis‐inducing effects are possibly due to BAX activation rather than Bcl‐2 inhibition as suggested by a recent study.