title: Synthesis and biological evaluation of α,β-unsaturated lactones as potent immunosuppressive agents.
abstract: Compounds having α,β-unsaturated lactones display a variety of biological activities. Many research groups have tested both natural and unnatural α,β-unsaturated lactones for as-yet undiscovered biological properties. We synthesized α,β-unsaturated lactones with various substituents at the δ-position and studied their immunosuppressive effects, that is, the inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized, the benzofuran-substituted α,β-unsaturated lactone 4h showed the best inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes (IC(50)=66.9 nM) without cytotoxicity at 10 μM. The results indicated that 4h may be useful as a potent immunosuppressive agent, as well as in IL-2-related studies.
authors.affiliation: Graduate Program of Medical System Engineering, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Won-Gil
authors.initials: WG
authors.lastname: Lee
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Hyojin
authors.initials: H
authors.lastname: Ko
mesh_terms: D003601:Cytotoxicity Tests, Immunologic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D007783:Lactones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007783:Lactones