Design and synthesis of novel 1,3,5-triphenyl pyrazolines as potential anti-inflammatory agents through allosteric inhibition of protein kinase Czeta (PKCζ).

ABSTRACT: Much light has been shed on the vital role of protein kinase Czeta (PKCζ) in NF-κB activation and the potential use of PKCζ inhibitors as anti-inflammatory agents. We previously reported a series of 1,3,5-trisubstituted pyrazolines as potent and selective allosteric inhibitors of PKCζ; in that series of compounds, the phenolic OH at the 5-phenyl was essential for binding to the PKCζ PIF pocket. In the present study, we surprisingly found that replacing it by a halogen and at the same time moving the OH to the 3-phenyl still resulted in active compounds. An extension of this class of compounds with a new focused library is presented herein, where the phenolic OH at the 5-phenyl, which was reported to be an irreplaceable feature for activity, was moved to the 3-phenyl and replaced by halogen

SUBMITTER: Abdel-Halim M 

PROVIDER: S-EPMC6072096 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature