Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid β plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation

Son, Seung Hwan; Min, Ji Young; Yoo, Ji Na; Lee, Hyun Woo; Kim, Nam Kwon; Yoo, Hyung Seok; Gee, Min Sung; Kim, Jong Ho; Seong, Ji Hye; Inn, Kyung‐Soo; Seo, Min‐Duk; Lee, Jong Kil

doi:10.1016/j.bioorg.2021.105022

Cited by 9 publications

(5 citation statements)

References 68 publications

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“…We decided to use 3-iodochromones rather than 3-bromo- or 3-chlorochromones for our study because the synthesis of the latter starting materials requires an additional step and we expected that they would be notably less reactive in the Suzuki–Miyaura coupling reaction . In contrast, 3-iodochromones 14 are conveniently available from enaminones via a slightly modified protocol originally published by Gammill .…”

Section: Resultsmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

et al. 2023

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Isoflavones were synthesized via Suzuki−Miyaura coupling of 3-iodochromones and para-methoxybenzene-and paraphenolboronic acid. In our hands, conditions commonly used for similar cross couplings turned out to be unsuccessful or difficult to reproduce, for example, due to the unplanned partial cleavage of MOM-protecting groups. Using Pd(dba) 2 as a precatalyst and tricyclohexylphosphine as an activating ligand, reliable cross-coupling conditions were identified. In all cases, notably higher yields of isoflavones were obtained with para-phenolboronic acid than with para-methoxybenzene boronic acid. This observation and the commercial availability of para-phenolboronic acid suggest that for the synthesis of the important 3′-prenyl-or 3′,5′-diprenylisoflavone substitution pattern a synthetic route that introduces the prenyl substituents after the Pd-catalyzed cross-coupling step, thereby avoiding laborious and protecting-group-intensive multistep syntheses of C-prenylated arene boronic acids, is advantageous.

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Section: Resultsmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

et al. 2023

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“…Aggregation of β -amyloid peptide (A β ) is one of the main histopathological hallmarks of AD [ 34 ]. Therefore, we selected the optimal compound 10a using a thioflavin T assay to determine the prevention of A β aggregation.…”

Section: Resultsmentioning

confidence: 99%

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Jia

et al. 2022

Molecules

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Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.

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“…Likewise, this flavonoid can inhibit activity on tau (τ) protein aggregates. Aβ and τ are two proteins in developing neurodegenerative diseases [77].…”

Section: Effect Of Phenolic Compounds In Models Of Neurodegeneration ...mentioning

confidence: 99%

Phenolic Compounds of Therapeutic Interest in Neuroprotection

Nájera-Maldonado,

Salazar,

Alvarez-Fitz

et al. 2024

JoX

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The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood–brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemia, and traumatic brain injury (TBI).

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Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid β plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation

Cited by 9 publications

References 68 publications

The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Phenolic Compounds of Therapeutic Interest in Neuroprotection

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