title: Synthesis and evaluation of 5-(3-(pyrazin-2-yl)benzylidene)thiazolidine-2,4-dione derivatives as pan-pim kinases inhibitors.
abstract: Pim kinases play a key role in the regulation of signaling pathways including proliferation, migration, and metabolism and are a potential target for cancer therapy. A series of 5-benzylidenethiazolidine-2,4-diones were synthesized as pim kinase inhibitors. The structure-activity relationships (SAR) of the analogues in inhibiting in vitro pim kinase activity as well as the proliferation of leukemia cell lines were examined. SAR studies indicated that a hydroxyl group at the 2-position of the benzene ring of 5-benzylidenethiazolidine-2,4-dione plays an important role in the inhibitory activity against all three pim kinases and replacement with a pyrazinyl group at the 5-position of the benzene ring of 5-benzylidenethiazolidine-2,4-dione improved activity significantly. The compounds exerted anti-proliferative activity against the three leukemia cell lines we tested. The most potent compound, 5i, had an EC₅₀ value of 0.8 µM in the MV4-11 cell line. The result of kinase profiling indicated that compound 5i was highly selective for pim-kinases.
authors: Department of Chemistry, Keimyung University.
authors: Jinho
authors: J
authors: Lee
authors: Jongseong
authors: J
authors: Park
authors: Victor Sukbong
authors: VS
authors: Hong
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D053778:Thiazolidines