Simplified bicyclic pyridinol analogues protect mitochondrial function

Bioorganic & Medicinal Chemistry
Xiaoqing CaiSidney M Hecht

Abstract

Bicyclic pyridinol antioxidants have been reported to suppress the autoxidation of methyl linoleate more effectively than α-tocopherol in benzene solution. A few novel lipophilic analogues have recently been synthesized by conjugating a pyridinol core with the phytyl side chain of α-tocopherol; these have been shown to possess potent antioxidant activity. However, the complexity of the synthetic routes has hampered their further development. Herein, we describe a facile approach, involving only five synthetic steps, to simplified analogues (1a-1c) and their acetate ester precursors (2a-2c). Simple alkyl chains of different lengths were attached to the 6-methyl group of the antioxidant core via regioselective metalation. These analogues were found to retain biological activity and exhibit protective behaviour under conditions of induced oxidative stress, which could lead to the development of more readily accessible analogues as potential antioxidants capable of preserving mitochondrial function.

References

May 11, 1984·Science·G W Burton, K U Ingold
Apr 1, 1994·Free Radical Biology & Medicine·P Ubezio, F Civoli
Feb 13, 2001·Trends in Biochemical Sciences·P BernardiM Forte
Dec 12, 2001·Seminars in Cell & Developmental Biology·I G Kirkinezos, C T Moraes
Mar 22, 2003·Current Opinion in Cell Biology·Toren Finkel
Mar 20, 2004·Nature Reviews. Drug Discovery·Kevin J BarnhamAshley I Bush
Apr 28, 2004·Advanced Drug Delivery Reviews·Panayiotis P ConstantinidesDean R Kessler
Mar 17, 2006·Free Radical Biology & Medicine·Marcelo G BoniniRonald P Mason
Nov 9, 2006·Free Radical Research·Earl R Stadtman

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Citations

Apr 1, 2014·European Journal of Medicinal Chemistry·Dong-Guk KimByeong-Seon Jeong
Feb 11, 2015·Free Radical Biology & Medicine·Bo Li, Derek A Pratt
Feb 6, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Diego MastroeniPaul D Coleman
Jun 6, 2014·ACS Medicinal Chemistry Letters·Omar M KhdourSidney M Hecht

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