Synthesis and biological evaluation of N-arylated-lactam-type iminosugars as potential immunosuppressive agents. Issue 28 (3rd July 2017)

• Record Type: Journal Article
• Authors: Liu, Hai-Qian; Song, Cheng-Cheng; Niu, You-Hong; Li, Tao; Li, Qin; Ye, Xin-Shan
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 28(2017)
• Page Start: 5912
• Page End: 5919
• Publication Date: 2017-07-03
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob01110e
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : New N -arylated iminosugar derivatives were designed and synthesized, leading to the identification of potent immunosuppressive agents. Abstract : Since the immunosuppressive agents currently used in clinics have significant side effects, it is very important to search for new effective and safe immunosuppressants. Iminosugars as a new class of immunosuppressants are less explored. In this report, 24 new N -arylated iminosugar derivatives, includingd -talo andd -galacto epimers, were designed and synthesized, and their immunosuppressive effects were evaluated by MTT assay. The experimental data demonstrated that compound20 showed the strongest inhibition effect (IC50 = 6.94 μM). Further studies revealed that the inhibitory effects on splenocyte proliferation may come from the suppression of both IFN-γ and IL-4 cytokines. The preliminary structure–activity relationship (SAR) analysis suggested that N -arylatedd -galacto-type iminosugars showed better inhibitory activities thand -talo-type analogues. The SAR analysis also showed that the inhibition effect of iminosugars can be improved by decreasing the polarity or increasing the hydrophobicity. These results may be beneficial to the discovery of new iminosugar derivatives as immunosuppressive agents.