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Three new iminosugar-containing KRN7000 (also referred to as α- GalCer) analogues were designed and synthesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar structures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifications. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRN7000 derivatives. [ABSTRACT FROM AUTHOR]

Iminosugars are an extremely interesting and versatile class of compounds and have many potential therapeutic applications. However, the use of iminosugar derivatives as immunomodulating agents is an area that is less explored. This review describes recent advances in the field of iminosugars as immunomodulating agents with a particular emphasis on 1-deoxynojirimycin analogues and related compounds. Both chemical and biological aspects concerning their preparation and/or occurrence in nature, as well as their immunomodulatory properties, are discussed. [ABSTRACT FROM AUTHOR]

We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of ′hit′ compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50=12-30 μ M) and low Jurkat cytotoxicities (IC50>100 μ M). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity. [ABSTRACT FROM AUTHOR]

The article discusses research being done on the pharmaceutical importance of iminosugars. It references a study published in the 2016 issue of "Organic Letters," by Professor Xin-Shan Ye et al., which examined the adoption of a method for the chemical synthesis of nitro-polyols and their applications in the iminosugar synthesis. The variables considered include iminosugars as immunosuppressive agents, the chirality of glycals and the nitration of glucal and scission of the carbon-carbon bond.

Graphical abstract Highlights • Synthesis of N -alkylated 1-deoxyfuconojirimycins as α-fucosidase inhibitors. • N -Decyl-1-deoxyfuconojirimycin was toxic towards various cancer cells. • Development of homology models for fucosidases from bovine and human origin. Abstract 1,5-Dideoxy-1,5-imino- l -fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N -alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The N -alkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N -Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N -alkyl DFJs studied. [ABSTRACT FROM AUTHOR]

Abstract: Iminosugars have gained a remarkable importance as new therapeutic agents since 1966. In this study, compounds A and B, two iminosugar analogs synthesized previously, showed an inhibition of the growth of K562 cells. They allowed cell cycle arrested at the G0/G1 phase, promoted apoptotic activities and also lowered the mitochondrial membrane potential. Further exploration of the apoptosis mechanism revealed that compound B significantly suppressed the expression of Hsp70, which is a major anti-apoptotic molecular chaperone. Significant decrease was also found in the expression of Akt, a serine/threonine-specific protein kinase with anti-apoptosis activities also known as protein kinase B (PKB). At mitochondria level in comparison with compound A, compound B brought a better promotion in the expression of pro-apoptotic protein Bad in Bcl-2 family. As a result of the promotion, the expression of anti-apoptotic protein Bcl-xL was down-regulated. Cytochrome c was released, activating the intrinsic signaling pathways of caspase and resulting in the occurrence of cascade reaction. In addition, compound B stimulated autophagy effectively by up-regulating Beclin 1, thus causing the conversion of LC3-I to LC3-II through Akt/mTOR signaling pathway. In summary, these results indicated that compounds A and B induced cell death through multiple pathways. The disclosed results not only provide an evidence of antitumor activity of iminosugars as a foundation for further studies, but also may find potential applications in chronic myeloid leukemia therapy as new heat shock protein inhibitors and autophagy inducer. [Copyright &y& Elsevier]

A versatile and concise synthesis of N-alkylated 1,4-dideoxy-1,4-imino-d-arabinitol and 1,4-dideoxy-1,4-imino-l-xylitol derivatives is described. These were prepared using pseudohemiketal lactams as key intermediates, which in turn were obtained from sucrose. The key intermediates were prepared by a diastereospecific tandem reaction which facilitated the introduction of various substituents on the nitrogen atom of the iminosugars. [ABSTRACT FROM AUTHOR]

Abstract: Several N-alkyl and hydroxyethyl-substituted iminosugar derivatives, including l-altro and d-galacto epimers, were synthesized and the effects of these synthetic iminosugars on proliferation of mouse splenocytes were evaluated in the MTT assay. The experimental data demonstrated that the N-alkylated d-galacto iminosugars showed better inhibitory activities than l-altro analogues, which might hold potential as immunosuppressive agents. [Copyright &y& Elsevier]

Highly potent N-substituted δ-lactams have been rationally designed and synthesized by a concise route with a one-pot tandem reaction as key step. These iminosugars show weak inhibition of wild-type β-glucocerebrosidase but 3- to 6-fold increases in mutant enzyme activity (N370S). [ABSTRACT FROM AUTHOR]