Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease

Seema Bag; Sanjukta Ghosh; Rekha Tulsan; Abha Sood; Weihong Zhou; Christine Schifone; Michelle Foster; Harry Levine; Béla Török; Marianna Török

doi:10.1016/j.bmcl.2013.02.103

Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease

Seema Bag, Sanjukta Ghosh, Rekha Tulsan, Abha Sood, Weihong Zhou, Christine Schifone, Michelle Foster, Harry Levine, Béla Török, Marianna Török

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.

Original language	English
Pages (from-to)	2614-2618
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2013.02.103
State	Published - May 1 2013

Bibliographical note

Funding Information:
Financial support provided by the University of Massachusetts Boston, and National Institute of Health ( R-15 AG025777-03A1 and R21AG028816-01 to H.L.) is gratefully acknowledged.

Keywords

Alzheimer's disease
Amyloid beta
Chalcones
Cholinesterase inhibition
Coumarins

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2013.02.103

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title = "Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease",

abstract = "A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.",

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note = "Funding Information: Financial support provided by the University of Massachusetts Boston, and National Institute of Health ( R-15 AG025777-03A1 and R21AG028816-01 to H.L.) is gratefully acknowledged. ",

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AU - Bag, Seema

AU - Ghosh, Sanjukta

AU - Tulsan, Rekha

AU - Sood, Abha

AU - Zhou, Weihong

AU - Schifone, Christine

AU - Foster, Michelle

AU - Levine, Harry

AU - Török, Béla

AU - Török, Marianna

N1 - Funding Information: Financial support provided by the University of Massachusetts Boston, and National Institute of Health ( R-15 AG025777-03A1 and R21AG028816-01 to H.L.) is gratefully acknowledged.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.

AB - A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent potential as multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.

KW - Alzheimer's disease

KW - Amyloid beta

KW - Chalcones

KW - Cholinesterase inhibition

KW - Coumarins

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JO - Bioorganic and Medicinal Chemistry Letters

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Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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