Evaluation of the Anti-Proliferative Activity of Rare Aldohexoses against MOLT-4F and DU-145 Human Cancer Cell Line and Structure-Activity Relationship of D-Idose

Abstract

D-Allose (D-All), a C-3 epimer of D-glucose (D-Glc), is a naturally rare monosaccharide, which shows anti-proliferative activity against several human cancer cell lines. Unlike conventional anticancer drugs, D-All targets glucose metabolism and is non-toxic to normal cells. Therefore, it has attracted attention as a unique “seed” compound for anticancer agents. However, the anti-proliferative activities of the other rare aldohexoses have not been examined yet. In this study, we evaluated the anti-proliferative activity of rare aldohexoses against human leukemia MOLT-4F and human prostate cancer DU-145 cell lines. We found that D-All and D-idose (D-Ido) at 5 mM inhibited cell proliferation of MOLT-4F cells by 46 % and 60 %, respectively. On the other hand, the rare aldohexoses at 5 mM did not show specific anti-proliferative activity against DU-145 cells. To explore the structure–activity relationship of D-Ido, we evaluated the anti-proliferative activity of D-sorbose (D-Sor), 6-deoxy-D-Ido, and L-xylose (L-Xyl) against MOLT-4F cells and found that D-Sor, 6-deoxy-D-Ido, and L-Xyl showed no inhibitory activity at 5 mM, suggesting that the aldose structure and the C-6 hydroxy group of D-Ido are important for its activity. Cellular glucose uptake assay and western blotting analysis of thioredoxin-interacting protein (TXNIP) expression suggested that the anti-proliferative activity of D-Ido is induced by inhibition of glucose uptake via TXNIP-independent pathway.

In silico molecular docking study of plant-based compounds from medicinal plant Lantana camara L. against Aedes aegypti L. protein

“…A study showed a rare sugar, D-Allose, possess anticancer effects [47,48,49,50,51] . It was also reported to have antiproliferative activity against MOLT-4F and DU-145 human cancer cell line [52] . Recently, 1H-Cycloprop[e]azulen-7-ol, decahydro-1, 1, 7-trimethyl-4-methylene-, [1ar-(1a.alpha.…”

C7 Epimerization of Benzylidene-Protected β-d-Idopyranosides Brings Structural Insights into Idose Conformational Flexibility

“…The biological relevance of idosides is further highlighted by the identification of 6-deoxy- l -idose in labdane-type diterpenes produced by Aster spathulifolius Caenorhabditis elegans, whereas d -idose was shown to exert an antiproliferative activity against leukemia cell lines . Moreover, l - glycero - d - ido -heptoses and 6-deoxy- d - ido -heptoses are found in the capsular polysaccharide (CPS) of Campylobacter jejuni HS:3 , and HS:4c, , respectively.…”

“…9 L-idose was also studied for its inhibitory effect against the growth of Caenorhabditis elegans, 10 whereas Didose was shown to exert an antiproliferative activity against leukemia cell lines. 11 Moreover, L-glycero-D-ido-heptoses and 6deoxy-D-ido-heptoses are found in the capsular polysaccharide (CPS) of Campylobacter jejuni HS:3 12,13 and HS:4c, 14,15 respectively.…”

“…Simultaneously, destabilization of the plausible α-triflate intermediate mediated by 1,3-syn-diaxial repulsion could enhance its reactivity toward the acceptors, thus favoring the formation of the β-glycosidic linkage. As shown in Table 2, coupling of thioidosyl donor 6a and 2adamantanol (11) under the promotion of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) in DCE was indeed β-stereoselective (β/α 6.6:1.0, entry 1). NMR identification of βand α-anomers 14a and 14c, respectively, was performed on the basis of the small coupling constants between protons H1, H2, H3, and H4, characteristic of their all-axial arrangement, and the 1 J C1,H1 (156 Hz for β, 171 Hz for α).…”

“…With 3-O-benzylated D-idoside 24 and 3-O-acetylated Dtaloside 28 in hand, both compounds were tested in various glycosylation conditions using 2-adamantanol (11) as the glycosyl acceptor (Table 4). In the case of the former compound, performing the reaction under the promotion of NIS/AgOTf in DCE led to a mixture of the corresponding βglycoside and its desilylated derivative (entry 1).…”