The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid β42 aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Imen Khelifi
- Audrey Tourrette
- Zohra Dhouafli
- Jalloul Bouajila
- Thomas Efferth
- Sara Abdelfatah
- Riadh Ksouri
- El Akrem Hayouni
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000513812100001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/bab.1870
- eISSN
- 1470-8744
- Externe Identifier
- Clarivate Analytics Document Solution ID: KM0MU
- PubMed Identifier: 31820491
- ISSN
- 0885-4513
- Zeitschrift
- BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
- Schlüsselwörter
- 2,3-dichloro,5,8-dihydroxy
- 1,4-naphthoquinone
- ABTS assay
- A beta(42) aggregation
- alginate microspheres
- anti-acetylcholinesterase assay
- molecular modelling
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid β<sub>42</sub> aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease
- Sub types
- Article
- Early Access
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Alzheimer's disease is characterized by amyloid β aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3‐dichloro‐5,8‐dihydroxy‐1,4‐naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aβ<jats:sub>42</jats:sub> aggregation. Such investigation was encouraged by the <jats:italic>in vitro</jats:italic> high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC<jats:sub>50</jats:sub> values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aβ<jats:sub>42</jats:sub> aggregation was evaluated by thioflavine‐T assay. Strong inhibition of Aβ<jats:sub>42</jats:sub> aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC<jats:sub>50</jats:sub> = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood–brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.</jats:p>
- Autoren
- Imen Khelifi
- Audrey Tourrette
- Zohra Dhouafli
- Jalloul Bouajila
- Thomas Efferth
- Sara Abdelfatah
- Riadh Ksouri
- El Akrem Hayouni
- DOI
- 10.1002/bab.1870
- eISSN
- 1470-8744
- ISSN
- 0885-4513
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Biotechnology and Applied Biochemistry
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 983 - 990
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/bab.1870
- Datum der Datenerfassung
- 2023
- Titel
- The antioxidant 2,3‐dichloro,5,8‐dihydroxy,1,4‐naphthoquinone inhibits acetyl‐cholinesterase activity and amyloid β<sub>42</sub> aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease
- Ausgabe der Zeitschrift
- 67
Data source: Crossref
- Abstract
- Alzheimer's disease is characterized by amyloid β aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aβ<sub>42</sub> aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC<sub>50</sub> values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aβ<sub>42</sub> aggregation was evaluated by thioflavine-T assay. Strong inhibition of Aβ<sub>42</sub> aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC<sub>50</sub> = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood-brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.
- Addresses
- Laboratory of Aromatic and Medicinal Plants, Biotechnology Center of Borj-Cedria, Hammam-Lif, Tunisia.
- Autoren
- Imen Khelifi
- Audrey Tourrette
- Zohra Dhouafli
- Jalloul Bouajila
- Thomas Efferth
- Sara Abdelfatah
- Riadh Ksouri
- El Akrem Hayouni
- DOI
- 10.1002/bab.1870
- eISSN
- 1470-8744
- Externe Identifier
- PubMed Identifier: 31820491
- Funding acknowledgements
- Tunisian Ministry of Higher Education and Scientific Research:
- Open access
- false
- ISSN
- 0885-4513
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Biotechnology and applied biochemistry
- Schlüsselwörter
- Humans
- Alzheimer Disease
- Naphthoquinones
- Acetylcholinesterase
- Peptide Fragments
- Cholinesterase Inhibitors
- Amyloid beta-Peptides
- GPI-Linked Proteins
- Protein Aggregates
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2020
- Paginierung
- 983 - 990
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Datum der Datenerfassung
- 2019
- Titel
- The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid β<sub>42</sub> aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 67
Data source: Europe PubMed Central
- Abstract
- Alzheimer's disease is characterized by amyloid β aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aβ42 aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC50 values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aβ42 aggregation was evaluated by thioflavine-T assay. Strong inhibition of Aβ42 aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC50 = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood-brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.
- Date of acceptance
- 2019
- Autoren
- Imen Khelifi
- Audrey Tourrette
- Zohra Dhouafli
- Jalloul Bouajila
- Thomas Efferth
- Sara Abdelfatah
- Riadh Ksouri
- El Akrem Hayouni
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31820491
- DOI
- 10.1002/bab.1870
- eISSN
- 1470-8744
- Funding acknowledgements
- Tunisian Ministry of Higher Education and Scientific Research:
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Biotechnol Appl Biochem
- Schlüsselwörter
- 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone
- ABTS assay
- Aβ42 aggregation
- alginate microspheres
- anti-acetylcholinesterase assay
- molecular modelling
- Acetylcholinesterase
- Alzheimer Disease
- Amyloid beta-Peptides
- Cholinesterase Inhibitors
- GPI-Linked Proteins
- Humans
- Naphthoquinones
- Peptide Fragments
- Protein Aggregates
- Sprache
- eng
- Country
- United States
- Paginierung
- 983 - 990
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid β42 aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 67
Data source: PubMed
- Beziehungen:
- Property of