Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition

Akihiko Hatano, Yuichi Kanno, Yuya Kondo, Yuta Sunaga, Hatsumi Umezawa, Munehiro Okada, Hideshi Yamada, Ren Iwaki, Atsushi Kato, Koji Fukui

Research output: Research - peer-reviewArticle

  • 2 Citations

Abstract

A series of five new fluorescent deoxynojirimycin (DNJ) conjugates were synthesized and evaluated for their inhibitory effect (IC50) on several α- and β-glucosidases. Three of the conjugates showed enhanced activity. The two synthetic conjugates, DNJ-CF3 1 and DNJ-Me 2, exhibited improved α-glucosidase inhibitory effects compared to DNJ and miglitol. Interestingly, conjugates 1 and 2 showed strong inhibition of almond-derived β-glucosidase, in contrast to the inhibition tendencies of other inhibitors. Conjugate 5 strongly inhibited rat intestinal maltase, even at 0.10 μM. A docking study indicated that all five conjugates bind to the active site of α-glucosidase (PDB: 3L4V, derived from Homo sapiens). The DNJ portion of the conjugate fits into the cavity of the enzyme, and the fluorescent part locates randomly on the outside surface. Thus, it is likely that these conjugates can specifically recognize intestinal cells, specifically the α-glucosidase on cell membranes.

LanguageEnglish
Pages773-778
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number2
DOIs
StatePublished - 2017 Jan 15

Fingerprint

alpha-Glucosidases
Derivatives
miglitol
1-Deoxynojirimycin
Cellulases
beta-Glucosidase
Cell membranes
Rats
Enzymes

Keywords

  • DNJ-fluorescent conjugate
  • Docking simulation
  • IC
  • Inhibitor
  • α-Glucosidase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition. / Hatano, Akihiko; Kanno, Yuichi; Kondo, Yuya; Sunaga, Yuta; Umezawa, Hatsumi; Okada, Munehiro; Yamada, Hideshi; Iwaki, Ren; Kato, Atsushi; Fukui, Koji.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 2, 15.01.2017, p. 773-778.

Research output: Research - peer-reviewArticle

Hatano, A, Kanno, Y, Kondo, Y, Sunaga, Y, Umezawa, H, Okada, M, Yamada, H, Iwaki, R, Kato, A & Fukui, K 2017, 'Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition' Bioorganic and Medicinal Chemistry, vol 25, no. 2, pp. 773-778. DOI: 10.1016/j.bmc.2016.11.053
Hatano, Akihiko ; Kanno, Yuichi ; Kondo, Yuya ; Sunaga, Yuta ; Umezawa, Hatsumi ; Okada, Munehiro ; Yamada, Hideshi ; Iwaki, Ren ; Kato, Atsushi ; Fukui, Koji. / Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 2. pp. 773-778
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