Triazolyl tryptoline derivatives as β-secretase inhibitors

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 language	English
Pages (from-to)	6572-6576
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2010.09.043
Publication status	Published - 15 Nov 2010
Externally published	Yes

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

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10.1016/j.bmcl.2010.09.043

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title = "Triazolyl tryptoline derivatives as β-secretase inhibitors",

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.",

keywords = "BACE1, BACE1 inhibitor, Binding mode, Cathepsin-D, Docking, Enzyme assay, JJCA-140, Tryptoline",

author = "Jutamas Jiaranaikulwanitch and Chantana Boonyarat and Fokin, {Valery V.} and Opa Vajragupta",

year = "2010",

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T1 - Triazolyl tryptoline derivatives as β-secretase inhibitors

AU - Jiaranaikulwanitch, Jutamas

AU - Boonyarat, Chantana

AU - Fokin, Valery V.

AU - Vajragupta, Opa

PY - 2010/11/15

Y1 - 2010/11/15

N2 - 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.

AB - 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.

KW - BACE1

KW - BACE1 inhibitor

KW - Binding mode

KW - Cathepsin-D

KW - Docking

KW - Enzyme assay

KW - JJCA-140

KW - Tryptoline

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