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1.
Biosci Biotechnol Biochem ; 83(12): 2194-2197, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31357905

ABSTRACT

The nematocidal activities of the fatty acid esters of d-allose were examined using the larvae of C. elegans. Among the fatty acid esters, 6-O-octanoyl-d-allose (3) showed significant activity. 6-O-octanoyl-d-glucose (5) showed no activity, indicating that the D-allose moiety is essential for the nematocidal activity of 3. A nonhydrolyzable alkoxy analog 6-O-octyl-d-allose (6) also showed activity equivalent to that of 3.


Subject(s)
Antinematodal Agents/pharmacology , Caenorhabditis elegans/growth & development , Glucose/pharmacology , Larva/drug effects , Animals , Glucose/chemistry
2.
Bioorg Med Chem Lett ; 29(17): 2483-2486, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31345631

ABSTRACT

The biological activities of deoxy sugars (deoxy monosaccharides) have remained largely unstudied until recently. We compared the growth inhibition by all 1-deoxyketohexoses using the animal model Caenorhabditis elegans. Among the eight stereoisomers, 1-deoxy-d-allulose (1d-d-Alu) showed particularly strong growth inhibition. The 50% inhibition of growth (GI50) concentration by 1d-d-Alu was estimated to be 5.4 mM, which is approximately 10 times lower than that of d-allulose (52.7 mM), and even lower than that of the potent glycolytic inhibitor, 2-deoxy-d-glucose (19.5 mM), implying that 1d-d-Alu has a strong growth inhibition. In contrast, 5-deoxy- and 6-deoxy-d-allulose showed no growth inhibition of C. elegans. The inhibition by 1d-d-Alu was alleviated by the addition of d-ribose or d-fructose. Our findings suggest that 1d-d-Alu-mediated growth inhibition could be induced by the imbalance in d-ribose metabolism. To our knowledge, this is the first report of biological activity of 1d-d-Alu which may be considered as an antimetabolite drug candidate.


Subject(s)
Caenorhabditis elegans/growth & development , Fructose/chemistry , Aldose-Ketose Isomerases/antagonists & inhibitors , Aldose-Ketose Isomerases/metabolism , Animals , Body Size/drug effects , Caenorhabditis elegans/drug effects , Deoxy Sugars/chemistry , Deoxy Sugars/pharmacology , Deoxyglucose/pharmacology , Drug Synergism , Fructose/pharmacology , Ribose/pharmacology , Stereoisomerism
3.
J Appl Glycosci (1999) ; 66(4): 139-142, 2019.
Article in English | MEDLINE | ID: mdl-34429692

ABSTRACT

D-Allose (D-All), C-3 epimer of D-glucose, is a rare sugar known to suppress reactive oxygen species generation and prevent hypertension. We previously reported that D-allulose, a structural isomer of D-All, prolongs the lifespan of the nematode Caenorhabditis elegans. Thus, D-All was predicted to affect longevity. In this study, we provide the first empirical evidence that D-All extends the lifespan of C. elegans. Lifespan assays revealed that a lifespan extension was induced by 28 mM D-All. In particular, a lifespan extension of 23.8 % was achieved (p < 0.0001). We further revealed that the effects of D-All on lifespan were dependent on the insulin gene daf-16 and the longevity gene sir-2.1, indicating a distinct mechanism from those of other hexoses, such as D-allulose, with previously reported antiaging effects.

4.
Biochem Biophys Res Commun ; 493(4): 1528-1533, 2017 12 02.
Article in English | MEDLINE | ID: mdl-28965946

ABSTRACT

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C. elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic.


Subject(s)
Caenorhabditis elegans/drug effects , Caloric Restriction/methods , Fructose/pharmacology , AMP-Activated Protein Kinases/metabolism , Animals , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans/physiology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Catalase/genetics , Catalase/metabolism , Eating/drug effects , Eating/genetics , Eating/physiology , Fructose/chemistry , Genes, Helminth , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Oxidative Stress/drug effects , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Receptors, Nicotinic/genetics , Receptors, Nicotinic/metabolism , Stereoisomerism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
5.
Biosci Biotechnol Biochem ; 80(6): 1058-61, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27022778

ABSTRACT

We compared the growth inhibitory effects of all aldohexose stereoisomers against the model animal Caenorhabditis elegans. Among the tested compounds, the rare sugars d-allose (d-All), d-talose (d-Tal), and l-idose (l-Ido) showed considerable growth inhibition under both monoxenic and axenic culture conditions. 6-Deoxy-d-All had no effect on growth, which suggests that C6-phosphorylation by hexokinase is essential for inhibition by d-All.


Subject(s)
Anthelmintics/pharmacology , Caenorhabditis elegans/drug effects , Glucose/pharmacology , Hexoses/pharmacology , Animals , Anthelmintics/chemistry , Axenic Culture , Caenorhabditis elegans/growth & development , Glucose/chemistry , Hexokinase/metabolism , Hexoses/chemistry , Phosphorylation , Structure-Activity Relationship
6.
Bioorg Med Chem Lett ; 26(3): 726-729, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26791015

ABSTRACT

Biological activities of unusual monosaccharides (rare sugars) have largely remained unstudied until recently. We compared the growth inhibitory effects of aldohexose stereoisomers against the animal model Caenorhabditis elegans cultured in monoxenic conditions with Escherichia coli as food. Among these stereoisomers, the rare sugar D-arabinose (D-Ara) showed particularly strong growth inhibition. The IC50 value for D-Ara was estimated to be 7.5 mM, which surpassed that of the potent glycolytic inhibitor 2-deoxy-D-glucose (19.5 mM) used as a positive control. The inhibitory effect of D-Ara was also observed in animals cultured in axenic conditions using a chemically defined medium; this excluded the possible influence of E. coli. To our knowledge, this is the first report of biological activity of D-Ara. The D-Ara-induced inhibition was recovered by adding either D-ribose or D-fructose, but not D-glucose. These findings suggest that the inhibition could be induced by multiple mechanisms, for example, disturbance of D-ribose and D-fructose metabolism.


Subject(s)
Arabinose/pharmacology , Caenorhabditis elegans/drug effects , Monosaccharides/chemistry , Monosaccharides/pharmacology , Animals , Arabinose/chemistry , Escherichia coli/drug effects , Inhibitory Concentration 50 , Stereoisomerism
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