Triazolyl tryptoline derivatives as β-secretase inhibitors

Jutamas Jiaranaikulwanitch, Chantana Boonyarat, Valery V. Fokin, Opa Vajragupta

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against BACE1 was used as a scaffold for the design of BACE1 inhibitors. The tryptoline was linked with different side chains by 1,2,3-triazole ring readily synthesized by catalytic azide-alkyne cycloaddition reactions. Twenty two triazolyl tryptoline derivatives were synthesized and screened for the inhibitory action against BACE1. JJCA-140 was the most potent inhibitor (IC50 = 1.49 μM) and was 100 times more selective for BACE1 than for Cat-D.

Original languageEnglish
Pages (from-to)6572-6576
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number22
DOIs
Publication statusPublished - 15 Nov 2010
Externally publishedYes

Fingerprint

Amyloid Precursor Protein Secretases
Derivatives
Triazoles
Alkynes
Azides
Cycloaddition
Cycloaddition Reaction
Scaffolds
Inhibitory Concentration 50
Screening
Cats
Databases
tryptoline

Keywords

  • BACE1
  • BACE1 inhibitor
  • Binding mode
  • Cathepsin-D
  • Docking
  • Enzyme assay
  • JJCA-140
  • Tryptoline

ASJC Scopus subject areas

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

Cite this

Jiaranaikulwanitch, J., Boonyarat, C., Fokin, V. V., & Vajragupta, O. (2010). Triazolyl tryptoline derivatives as β-secretase inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(22), 6572-6576. https://doi.org/10.1016/j.bmcl.2010.09.043

Triazolyl tryptoline derivatives as β-secretase inhibitors. / Jiaranaikulwanitch, Jutamas; Boonyarat, Chantana; Fokin, Valery V.; Vajragupta, Opa.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 22, 15.11.2010, p. 6572-6576.

Research output: Contribution to journalArticle

Jiaranaikulwanitch, J, Boonyarat, C, Fokin, VV & Vajragupta, O 2010, 'Triazolyl tryptoline derivatives as β-secretase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 22, pp. 6572-6576. https://doi.org/10.1016/j.bmcl.2010.09.043
Jiaranaikulwanitch, Jutamas ; Boonyarat, Chantana ; Fokin, Valery V. ; Vajragupta, Opa. / Triazolyl tryptoline derivatives as β-secretase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 22. pp. 6572-6576.
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