Design, synthesis and biological evaluation of novel O-substituted tryptanthrin oxime derivatives as c-Jun N-terminal kinase inhibitors.

ABSTRACT: The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNK represents an attractive target for therapeutic intervention. Herein, a panel of novel tryptanthrin oxime analogs were synthesized and evaluated for JNK1-3 binding (K_d) and inhibition of cellular inflammatory responses (IC₅₀). Several compounds exhibited submicromolar JNK binding affinity, with the most potent inhibitor being 6-(acetoxyimino)indolo[2,1-b]quinazolin-12(6H)-one (1j), which demonstrated high JNK1-3 binding affinity (K_d = 340, 490, and 180 nM for JNK1, JNK2, and JNK3, respecti

SUBMITTER: Schepetkin IA 

PROVIDER: S-EPMC9510750 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature