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

• Published in: Carbohydrate research 2022-01, Vol.511, p.108479-108479, Article 108479
• Main Authors: Thangarasu, Arun K., Sambyal, Shainy, Kumar, Halmuthur Mahabalarao Sampath, Lankalapalli, Ravi S.
• Format: Article
• Language: English
• Subjects: C-glycoside; Iminosugar; Immunomodulation; Immunopotentiation; Nojirimycin
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2021.108479

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. [Display omitted] •Three distinct classes of novel iminosugar nojirimycin analogues were synthesized for immunological studies.•First report demonstrating multiple variations of iminosugar analogues with a focussed library.•The novel iminosugar analogues exhibited an unprecedented immunopotentiating activities.•Structural changes in iminosugar analogues profoundly alter the immunomodulatory properties.