New imidazoles as probes of the active site topology and potent inhibitors of β-glucosidase

Yaw-Kuen Li*, Hsuan-Shn Hsu, Li Fen Chang, Genly Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Series of 4-arylimidazoles, ω-N-acylhistamines and 4-(ω-phenylalkyl) imidazoles were synthesized in order to probe the active site topology of sweet almond β-glucosidase. These imidazole derivatives were shown to be very powerful competitive inhibitors. Among the 20 tested compounds, ω-N-benzoylhistamine and 4-(3'-phenylpropyl)imidazole are the most potent inhibitors of the enzyme, with pH-independent K(i) values of 0.06 and 0.07 μM, respectively. The inhibition of 4-(ω-phenylalkyl)imidazoles exhibited an interesting trend as to K(i) values: 4-phenylimidazole (6.6 μM) > 4-benzylimidazole (1.4 μM) > 4-(2'-phenylethyl)imidazole (0.82 μM)> 4-(3'-phenylpropyl)imidazole (0.07 μM) < 4-(4'-phenylbutyl)imidazole (0.13 μM)< 4-(5'-phenylpentyl) imidazole (0.3 μM). This revealed that the imidazole and aryl binding sites (which result from favorable interactions within the corresponding glycone and aglycone binding subsites) are separated by the optimal distance equivalent to the length of a -CH2-CH2-CH2- group. Substitutions of the phenyl moieties of 4-phenylimidazole and 4-benzoylhistamine result in weaker inhibition. These classes of imidazoles are particularly powerful inhibitors of sweet almond β-glucosidase.

Original languageAmerican English
Pages (from-to)416-422
Number of pages7
JournalJournal of Biochemistry
Volume123
Issue number3
DOIs
StatePublished - Mar 1998

Keywords

  • 4-(ω-phenylalkyl) imidazoles
  • 4-Arylimidazoles
  • Inhibition
  • β-glucosidase
  • ω-N-acylhistamines

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