Design, synthesis, and preliminary immunopotentiating activity of new analogues of nojirimycin

Abstract

Three new classes of nojirimycin analogues viz. N-alkyl with C1-substituent (4-phenylbutyl), N-substituted 1-deoxynojirimycin and its congener δ-lactam, and a 4-phenylbutyl-β-C-glycoside were designed and synthesized for immunological studies. The resulting diverse compound library exhibited proliferation of B Cells and T cells induced by LPS and Con A, respectively. The majority of the analogues augmented the secretion of IL-12 in dendritic cells and TNF-α secretion in murine peritoneal macrophages compared to LPS (10 μg/ml). A deoxynojirimycin-triazole conjugate of phytosphingosine analogue was superior in the responses mentioned above and exhibited nitric oxide response equal to LPS. In comparison to findings on its congeners with immunosuppressive action, early immunological tests show that the novel nojirimycin analogues have immunopotentiating effect. Hence, nojirimycin analogues offer tremendous potential in tuning the immunomodulatory activity of iminosugars by subtle to substantial structural variations.

Keywords: C-glycoside; Iminosugar; Immunomodulation; Immunopotentiation; Nojirimycin.