Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model

Alzheimer’s Disease (AD) is the most common form of dementia in individuals over the age of 65. There is no known prevention for the progression of the disease, although the FDA recently approved two drugs for AD. The exact etiology of AD is still under debate; however, it is commonly associated wit...

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Main Authors: Aadya Jaipuria, Madison Castillo, James Boksanski, Greg Landry, Ji Hyung Beak, Michelle Young, David T. Priefer, Kaïs Guessab, Crystal N. Ellis, Ronny Priefer
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Chemistry
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Online Access:https://www.mdpi.com/2624-8549/6/6/89
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author Aadya Jaipuria
Madison Castillo
James Boksanski
Greg Landry
Ji Hyung Beak
Michelle Young
David T. Priefer
Kaïs Guessab
Crystal N. Ellis
Ronny Priefer
author_facet Aadya Jaipuria
Madison Castillo
James Boksanski
Greg Landry
Ji Hyung Beak
Michelle Young
David T. Priefer
Kaïs Guessab
Crystal N. Ellis
Ronny Priefer
author_sort Aadya Jaipuria
collection DOAJ
description Alzheimer’s Disease (AD) is the most common form of dementia in individuals over the age of 65. There is no known prevention for the progression of the disease, although the FDA recently approved two drugs for AD. The exact etiology of AD is still under debate; however, it is commonly associated with the aggregation of amyloid-beta (Aβ) plaques in the brain. Recently some extended chalcones were reported to be potential anti-amyloidogenic agents. In this study, a larger library of extended chalcone analogs were synthesized with modifications on both rings. These were tested using the Thioflavin T fluorescence assay to measure their anti-Aβ aggregation properties. Three notably active compounds were further evaluated for potential neurotoxicity and neuroprotection using an MTT cell viability assay. These compounds were non-neurotoxic and displayed a trend toward neuroprotection. These were further assessed in a <i>Drosophila melanogaster</i> animal AD model. A forced climbing assay revealed statistically significant changes in flies’ movement by ~30% when fed these anti-amyloidogenic agents.
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spelling doaj-art-45cbbdaf4d1646839ba1243a3e32c2112025-08-20T02:00:35ZengMDPI AGChemistry2624-85492024-11-01661477149410.3390/chemistry6060089Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease ModelAadya Jaipuria0Madison Castillo1James Boksanski2Greg Landry3Ji Hyung Beak4Michelle Young5David T. Priefer6Kaïs Guessab7Crystal N. Ellis8Ronny Priefer9Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAMassachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USAAlzheimer’s Disease (AD) is the most common form of dementia in individuals over the age of 65. There is no known prevention for the progression of the disease, although the FDA recently approved two drugs for AD. The exact etiology of AD is still under debate; however, it is commonly associated with the aggregation of amyloid-beta (Aβ) plaques in the brain. Recently some extended chalcones were reported to be potential anti-amyloidogenic agents. In this study, a larger library of extended chalcone analogs were synthesized with modifications on both rings. These were tested using the Thioflavin T fluorescence assay to measure their anti-Aβ aggregation properties. Three notably active compounds were further evaluated for potential neurotoxicity and neuroprotection using an MTT cell viability assay. These compounds were non-neurotoxic and displayed a trend toward neuroprotection. These were further assessed in a <i>Drosophila melanogaster</i> animal AD model. A forced climbing assay revealed statistically significant changes in flies’ movement by ~30% when fed these anti-amyloidogenic agents.https://www.mdpi.com/2624-8549/6/6/89Alzheimer’s Diseaseanti-amyloidogenicextended chalconesneuroprotection
spellingShingle Aadya Jaipuria
Madison Castillo
James Boksanski
Greg Landry
Ji Hyung Beak
Michelle Young
David T. Priefer
Kaïs Guessab
Crystal N. Ellis
Ronny Priefer
Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
Chemistry
Alzheimer’s Disease
anti-amyloidogenic
extended chalcones
neuroprotection
title Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
title_full Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
title_fullStr Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
title_full_unstemmed Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
title_short Extended Chalcones: Synthesis, In Vitro Analysis, and In Vivo Testing Against a <i>Drosophila melanogaster</i> Alzheimer’s Disease Model
title_sort extended chalcones synthesis in vitro analysis and in vivo testing against a i drosophila melanogaster i alzheimer s disease model
topic Alzheimer’s Disease
anti-amyloidogenic
extended chalcones
neuroprotection
url https://www.mdpi.com/2624-8549/6/6/89
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