Abstract:
:The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immunosuppressive activity was evaluated by measuring suppression of IL-2 release from activated Jurkat T cells. Optimizing the three side chains around the quinolinone skeleton revealed the most active compound: 11l. This compound exhibits potent inhibitory activity toward IL-2 release in both 12-o-tetradecanoylphorbol-13-acetate (PMA)/A23187 (ionomycin) (IC50=80±10nM) and anti-CD3/CD28-stimulated Jurkat T cells (83% inhibition at 10μM) without cytotoxic effects. Further investigation into the underlying mechanism of 11l indicated the suppression of NF-κB and nuclear factor of activated T cells (NFAT) promoter activities in Jurkat T cells.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Kwak SH,Kang JA,Kim M,Lee SD,Park JH,Park SG,Ko H,Kim YCdoi
10.1016/j.bmc.2016.08.051subject
Has Abstractpub_date
2016-11-01 00:00:00pages
5357-5367issue
21eissn
0968-0896issn
1464-3391pii
S0968-0896(16)30668-Xjournal_volume
24pub_type
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