Radiosynthesis and whole‐body distribution in mice of a 18F‐labeled azepino[4,3‐b]indole‐1‐one derivative with multimodal activity for the treatment of Alzheimer's disease
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Le résumé fourni par la source
Abstract Recently, the azepino[4,3‐b]indole‐1‐one derivative 1 showed in vitro nanomolar inhibition against butyrylcholinesterase (BChE), the ChE isoform that plays a role in the progression and pathophysiology of Alzheimer's disease (AD), and protects against N‐methyl‐ d‐aspartate‐induced neuronal toxicity. Three 9‐R‐substituted (R = F, Br, OMe) congeners were investigated. The 9‐F derivative (2a) was found more potent as BChE inhibitors (half‐maximal inhibitory concentration value = 21 nM) than 2b (9‐Br) and 2c (9‐OMe), achieving a residence time (38 s), assessed by surface plasmon resonance, threefold higher than that of 1. To progress in featuring the in vivo pharmacological characterization of 2a, herein the 18F‐labeled congener 2a was synthesized, by applying the aromatic 18F‐fluorination method, and its whole‐body distribution in healthy mice, including brain penetration, was evaluated through positron emission tomography imaging. [18F]2a exhibited a rapid and high brain uptake (3.35 ± 0.26% ID g−1 at 0.95 ± 0.15 min after injection), followed by a rapid clearance (t1/2 = 6.50 ± 0.93 min), showing good blood–brain barrier crossing. After a transient liver accumulation of [18F]2a, the intestinal and urinary excretion was quantified. Finally, ex vivo pharmacological experiments in mice showed that the unlabeled 2a affects the transmitters' neurochemistry, which might be favorable to reverse cognition impairment in mild‐to‐moderate AD‐related dementias.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Radiosynthesis and whole‐body distribution in mice of a <sup>18</sup>F‐labeled azepino[4,3‐<i>b</i>]indole‐1‐one derivative with multimodal activity for the treatment of Alzheimer's disease
- Date Crossref
- 29/12/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Seoul National University Bundang Hospital Department of Nuclear Medicine pays non établi dans la noticeÉtablissement de santé
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University of Bari Aldo Moro pays non établi dans la noticeUniversité ou école supérieure
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University of Foggia pays non établi dans la noticeUniversité ou école supérieure
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Advanced Institute of Convergence Technology pays non établi dans la noticeStructure de recherche
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Center for Nanomolecular Imaging and Innovative Drug Development Advanced Institutes of Convergence Technology Suwon Republic of Korea pays non établi dans la noticeStructure de recherche
Department of Nuclear Medicine — Seoul National University Bundang Hospital, University of Bari Aldo Moro et University of Foggia, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.