Growth inhibition by 1-deoxy-d-allulose, a novel bioactive deoxy sugar, screened using Caenorhabditis elegans assay

Bioorg Med Chem Lett. 2019 Sep 1;29(17):2483-2486. doi: 10.1016/j.bmcl.2019.07.017. Epub 2019 Jul 16.

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.

Keywords: 1-Deoxy-d-allulose; Caenorhabditis elegans; Deoxy sugar; Growth inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldose-Ketose Isomerases / antagonists & inhibitors
  • Aldose-Ketose Isomerases / metabolism
  • Animals
  • Body Size / drug effects
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / growth & development*
  • Deoxy Sugars / chemistry
  • Deoxy Sugars / pharmacology
  • Deoxyglucose / pharmacology
  • Drug Synergism
  • Fructose / chemistry*
  • Fructose / pharmacology
  • Ribose / pharmacology
  • Stereoisomerism

Substances

  • Deoxy Sugars
  • psicose
  • Fructose
  • Ribose
  • Deoxyglucose
  • Aldose-Ketose Isomerases
  • ribosephosphate isomerase