Mono-and hepta-antennated C-6 branched glycosylthioureido-cyclomaltoheptaose derivatives have been prepared efficiently by reaction, at ambient temperature, of b-d-glycopyranosyl isothiocyanates in the glucopyranose, cellobiose, and lactose series with either 6 I -amino-6 I -deoxycyclomaltoheptaose in pyridine or heptakis(6-amino-6-deoxy)cyclomaltoheptaose in water ± acetone at pH 8. The reverse strategy, which involves the corresponding glycosylamines as nucleophiles in reaction with cyclomaltoheptaose isothiocyanates, proved less satisfactory resulting in a number of by-products which hampered the purification step. The synthetic scheme was extended to alkyl and aryl isothiocyanate, electrophiles which as functional groups are of interest for the elaboration of dendritic wedges and the modification of the interaction and inclusion properties of cyclodextrins.

Aberrant glycosylation changes on many glycoproteins are often related to cancer progression and metastasis. sp -Iminosugar-type castanospermine analogues, inhibitors of α-glucosidases, have been reported to exhibit antitumor activity. However, their effects on cell migration and the underlying molecular mechanism are not fully understood. Here, we investigated the effect of the pseudo-C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives (CO-OCS) on breast cancer cells (MCF-7 and MDA-MB-231 cells), and MCF-10A mammary normal cell lines. We showed that CO-OCS treatment results in the drastic decrease of breast cancer cell migration without affecting cell proliferation. Furthermore, CO-OCS significantly reduced both the expression of β1-integrin, which is a crucial interacting partner of Focal Adhesion Kinase (FAK), and the phosphorylation rates of FAK and ERK1/2. CO-OCS also drastically reduced Ca entry through Store Operated Channels (SOC). Orai1 and Stim1, two N-glycosylated proteins, are involved in Store-Operated Calcium Entry (SOCE), and are essential for breast tumor cell migration. Our results showed that CO-OCS decreased the expression, at the protein level, of Stim1 without affecting that of Orai1. Moreover, cell migration and SOCE were attenuated by CO-OCS as well as when Stim1 was silenced. In contrast, in MCF-10A cells, CO-OCS slightly reduced cell migration, but was without effect on gene expression of Stim1, Orai1, β1-integrin, or FAK and ERK1/2 activation. Our results provide strong evidence for a significant effect of CO-OCS on breast cancer cell migration and support that this effect was associated with β1-integrin, Stim1, and FAK signaling pathways.

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The sulfur‐linked pentathiohexasaccharide 3I,3IV‐di‐β‐D‐glucopyranosylthiogentiotetraose (12) has been prepared by a convergent approach involving the reaction of 1,2,4‐tri‐O‐acetyl‐6‐deoxy‐6‐iodo‐3‐S‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐3‐thio‐β‐D‐glucopyranose (10) with the sodium salt of 2,3,4‐tri‐O‐acetyl‐6‐S‐[2,4‐di‐O‐acetyl‐3,6‐di‐S‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐3,6‐dithio‐β‐D‐glucopyranosyl]‐1,6‐dithio‐β‐D‐glucopyranose (4). A further reaction, involving the sodium salt of the peracetylated β‐1‐thio derivative of 12 with 1,2,3,4‐tetra‐O‐acetyl‐6‐deoxy‐6‐iodo‐β‐D‐glucopyranose (26), afforded the homologous sulfur‐linked hexathioheptasaccharide 3II,3V‐di‐β‐D‐glucopyranosylthiogentiopentaose (28). Related sulfur‐linked positional isomers 3II,3IV‐di‐D‐β‐glucopyranosylthiogentiotetraose (34) and 3III,3V‐di‐β‐D‐glucopyranosylthiogentiopentaose (39) have been prepared using analogous synthetic strategies. Thus, SN2 displacement of the iodine atom in 10 by the sodium salt of 2,4‐di‐O‐acetyl‐3,6‐di‐S‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐1,3,6‐trithio‐β‐D‐glucopyranose afforded a tetrathiopentasaccharide, which resulted in the pentathiohexasaccharide 34 by a sequence of reactions involving the 1‐thioglycose 32 in reaction with 26. The hexathioheptasaccharide 39 was obtained conveniently by the reaction of 26 with the acetylated 1‐thio‐6I, 3II, 6II, 3IV, 6IV‐pentathio derivative 37, followed by deacylation. The four isomeric pentathiohexa‐ and hexathioheptasaccharides 12,34 and 28,39, respectively, were all found to be active in eliciting phytoalexin accumulation in soybean cotyledon tissue and in binding to a glucan‐binding protein of soybean, although to a lesser extent than the corresponding O‐oligosaccharides, the alternate thiohexa‐ and thioheptasaccharides 12,28 being more active as compared to the geminally branched isomers 34,39.