Synthesis and biological evaluation of α, β-unsaturated lactones as potent immunosuppressive agents

Compounds having alpha,beta-unsaturated lactones display a variety of biological activities. Many research groups have tested both natural and unnatural alpha,beta-unsaturated lactones for as-yet undiscovered biological properties. We synthesized alpha,beta-unsaturated lactones with various substituents at the delta-position and studied their immunosuppressive effects, that is, the inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized, the benzofuran-substituted alpha,beta-unsaturated lactone 4h showed the best inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes (IC50 = 66.9 nM) without cytotoxicity at 10 mu M. The results indicated that 4h may be useful as a potent immunosuppressive agent, as well as in IL-2-related studies. (C) 2011 Elsevier Ltd. All rights reserved.