Divergent synthesis of biflavonoids yields novel inhibitors of the aggregation of amyloid β (1-42)

Organic & Biomolecular Chemistry
Tze Han SumDavid R Spring

Abstract

Biflavonoids are associated with a variety of biologically useful properties. However, synthetic biflavonoids are poorly explored within drug discovery. There is considerable structural diversity possible within this compound class and large regions of potentially biologically relevant biflavonoid chemical space remain untapped or underexplored. Herein, we report the development of a modular and divergent strategy towards biflavonoid derivatives which enabled the step-economical preparation of a structurally diverse collection of novel unnatural biflavonoids. Preliminary studies established that the strategy could also be successfully extended to the preparation of very rare triflavonoids, which are also expected to be useful tools for biological intervention. Prompted by previous inhibitory studies with flavonoid libraries, amyloid anti-aggregation screening was performed, which led to the identification of several structurally novel inhibitors of the aggregation of the amyloid β peptide (Aβ42). Aggregated Aβ42 is a pathological hallmark of Alzheimer's disease and the use of small molecules to inhibit the aggregation process has been identified as a potentially valuable therapeutic strategy for disease treatment. Methylated bi...Continue Reading

References

May 1, 1970·Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft·G Wurm, H Loth
Dec 17, 2004·Nature·Christopher M Dobson
Dec 17, 2004·Nature·Christopher Lipinski, Andrew Hopkins
Oct 19, 2005·Journal of Computer-aided Molecular Design·Igor V TetkoVolodymyr V Prokopenko
Mar 1, 2006·Bioorganic & Medicinal Chemistry Letters·Jianjun ChenHaeil Park
Mar 28, 2006·Journal of Natural Products·Zakaria H MbwamboLuc Pieters
Apr 1, 2006·Bioorganic & Medicinal Chemistry Letters·Mi Kyeong LeeYoung Choong Kim
Mar 3, 2007·The Journal of Pharmacy and Pharmacology·Haeil ParkHyun Pyo Kim
Nov 21, 2007·Chemistry & Biodiversity·Mohammed RahmanUmesh R Desai
Apr 15, 2008·Archives of Pharmacal Research·Hyun Pyo KimSam Sik Kang
May 31, 2008·Nature Structural & Molecular Biology·Dagmar E EhrnhoeferErich E Wanker
Dec 2, 2008·Chemical & Pharmaceutical Bulletin·Shuang LiangShi-Kai Yan
Sep 16, 2009·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·William M Pardridge
Jan 29, 2010·The New England Journal of Medicine·Henry W Querfurth, Frank M LaFerla
May 1, 2010·Nature Reviews. Drug Discovery·Martin Citron
Jun 29, 2010·Journal of Combinatorial Chemistry·Joel AlvimArlene G Corrêa
Jul 9, 2010·Nature Reviews. Drug Discovery
Oct 29, 2010·Nature Communications·Takashi UemuraSusumu Kitagawa
Nov 26, 2010·The Journal of Biological Chemistry·Ali Reza A LadiwalaPeter M Tessier
Dec 31, 2010·Archives of Pharmacal Research·Santosh K GurungHaeil Park
Jan 26, 2011·ACS Chemical Biology·David J HugginsDavid R Spring
May 3, 2011·Bioorganic & Medicinal Chemistry·Gabriel SagreraGustavo Seoane
Apr 25, 2013·Journal of the American Chemical Society·Fernando L PalhanoJeffery W Kelly
Jun 15, 2013·International Journal of Molecular Sciences·Massimo Stefani, Stefania Rigacci
Dec 20, 2013·Expert Opinion on Drug Discovery·José L Medina-FrancoNathalie Meurice
Mar 28, 2016·European Journal of Medicinal Chemistry·Amel MeguellatiMarine Peuchmaur
Sep 21, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tze Han SumDavid R Spring
Dec 3, 2016·Nature·Alison Abbott, Elie Dolgin
Dec 30, 2016·Future Science OA·Ruth MacLeodGeorge S Baillie
Mar 25, 2017·Journal of Medicinal Chemistry·Shiao Y Chow, Adam Nelson

❮ Previous
Next ❯

Citations

Apr 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Immo SerbianRené Csuk
Jan 26, 2021·The Science of the Total Environment·José C J M D S Menezes, Vinícius R Campos
Feb 2, 2021·Results in Chemistry·Yustina HartiniMaywan Hariono

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Related Papers

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Tze Han SumDavid R Spring
CNS & Neurological Disorders Drug Targets
Margarita E NeganovaGjumrakch Aliev
© 2022 Meta ULC. All rights reserved