PET imaging of nobiletin based on a practical total synthesis

Asakawa, Tomohiro; Hiza, Aiki; Nakayama, Miho; Inai, Makoto; Oyama, Dai; Koide, Hiroyuki; Shimizu, Kosuke; Wakimoto, Toshiyuki; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto; Kan, Toshiyuki

doi:10.1039/c0cc04936k

Cited by 45 publications

(24 citation statements)

References 14 publications

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“…Notably, analyses using high-performance liquid chromatography (HPLC) and positron emission tomography (PET) suggest nobiletin penetrates the BBB and reaches a maximal level within 3-5 min after peripheral administration 70,71). Additionally, 4'-demethylnobiletin, a major urinary metabolite of nobiletin in rats and mice,72,73) can cross the BBB and exert memory-improving effects in the brain 74)…”

Section: Resultsmentioning

confidence: 99%

Anti-dementia Activity of Nobiletin, a Citrus Flavonoid: A Review of Animal Studies

Nakajima

Ohizumi

Yamada

2014

Clin Psychopharmacol Neurosci

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Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function and has a detrimental impact worldwide. Despite intensive laboratory and clinical research over the last three decades, pharmacological options for the prevention and effective long-term treatment of AD are not currently available. Consequently, successful therapeutic and preventive treatments for AD are needed. When researching materials from natural resources having anti-dementia drug activity, we identified nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin exhibited memory-improving effects in various animal models of dementia and exerted a wide range of beneficial effects against pathological features of AD including amyloid-β (Aβ) pathology, tau hyperphosphorylation, oxidative stress, cholinergic neurodegeneration and dysfunction of synaptic plasticity-related signaling, suggesting this natural compound could become a novel drug for the treatment and prevention of AD.

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Section: Resultsmentioning

confidence: 99%

Anti-dementia Activity of Nobiletin, a Citrus Flavonoid: A Review of Animal Studies

Nakajima

Ohizumi

Yamada

2014

Clin Psychopharmacol Neurosci

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“…Thus, the phenolic OH should be at position 2 in ring A. This demethylation reaction vicinal to the ketone during Friedel-Crafts acylations has been described by other authors [25][26][27]. By changing the catalyst, the reaction could be selectively directed towards each of these two compounds.…”

Section: Chemistrymentioning

confidence: 74%

Conformational mimetics of the α-methyl chalcone TUB091 binding tubulin: Design, synthesis and antiproliferative activity

Bueno

Tobajas

Quesada

et al. 2018

European Journal of Medicinal Chemistry

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Based on the conformation of the α-methyl chalcone TUB091 in its complex with tubulin, a series of conformational mimetics have been designed and synthesized where the methyl group of the chalcone has been fused to phenyl ring B resulting in 1,2,3,4-tetrahydronaphthalen-2-yl aryl ketones. Among the synthesized compounds, the 5-amino-6-methoxy derivative, with a similar substitution pattern to that of TUB091, showed antiproliferative activity around 20 nM against tumor and endothelial cells. Tubulin binding experiments confirmed its binding to tubulin at the colchicine site with a Kb of 2.4 × 10 M resulting in the inhibition of the in vitro assembly of purified tubulin. Moreover, based on the recently reported complex of combretastatin A4 (CA4) with tubulin, a comparative analysis of the binding mode of CA4 and the α-methyl chalcone to tubulin has been performed.

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“…The 1 H NMR data are in very close agreement with the natural and synthetic compound. 1 was also synthesised as a precursor to the synthesis of the Citrus polymethoxylated flavone nobiletin in a study of its use as a stimulator of neuronal cell signalling by positron emission tomography (Asakawa et al, 2011).…”

Section: Resultsmentioning

confidence: 99%