Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer's disease.

Bioorganic & Medicinal Chemistry Letters
John SaathoffShijun Zhang

Abstract

In our continuing efforts to develop novel neuroprotectants for Alzheimer's disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH3 on the indole ring of the lead compound. The results also demonstrated that the β-keto moiety can be modified to retain or improve the neuroprotective activity. Docking studies of selected analogs to the FMN site of mitochondrial complex I also supported the observed neuroprotective activities. Collectively, the results provide further information to guide optimization and development of analogs based on this chemical scaffold as neuroprotectants with a novel mechanism of action for AD.

References

Mar 27, 2004·Physiological Reviews·Jesus AvilaFelix Hernandez
Jul 3, 2007·Cellular and Molecular Life Sciences : CMLS·X ZhuG Perry
Jan 23, 2008·Journal of Neurochemistry·Yuanbin LiuDavid Schubert
Feb 1, 2008·Journal of Medicinal Chemistry·Alessio AmadasiGlen E Kellogg
Jul 22, 2008·Neurobiology of Aging·Pamela MaherKazuho Abe
Oct 28, 2008·Journal of Alzheimer's Disease : JAD·Ashley I Bush
Jul 29, 2009·The Journal of Biological Chemistry·John M Berrisford, Leonid A Sazanov
Jul 23, 2011·Bioorganic & Medicinal Chemistry·Luba DubinskyMichael M Meijler
Jul 4, 2012·Journal of Neuroinflammation·Dimitrije KrsticIrene Knuesel
Jul 24, 2012·Biochemical Society Transactions·Sarah M WardLester I Binder
Jul 27, 2012·Bioorganic & Medicinal Chemistry·Yun Suk LeeKye Jung Shin
Jan 8, 2013·ACS Medicinal Chemistry Letters·Kai LiuShijun Zhang
Nov 6, 2013·Biochimica Et Biophysica Acta·Xinglong WangXiongwei Zhu
Mar 31, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·John M SaathoffShijun Zhang
May 18, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Valeria Calsolaro, Paul Edison
Jun 4, 2019·Bioorganic & Medicinal Chemistry Letters·Liu HeShijun Zhang

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Citations

Nov 24, 2021·ACS Chemical Neuroscience·Yulong XuShijun Zhang

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