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Multiple reactivities of flavonoids towards pathological elements in Alzheimer's disease: structure-activity relationship.

ABSTRACT: Amyloid-β (Aβ) accumulation, metal ion dyshomeostasis, oxidative stress, and cholinergic deficit are four major characteristics of Alzheimer's disease (AD). Herein, we report the reactivities of 12 flavonoids against four pathogenic elements of AD: metal-free and metal-bound Aβ, free radicals, and acetylcholinesterase. A series of 12 flavonoids was selected based on the molecular structures that are responsible for multiple reactivities including hydroxyl substitution and transfer of the B ring from C2 to C3. Our experimental and computational studies reveal that the catechol moiety, the hydroxyl groups at C3 and C7, and the position of the B ring are important for instilling multiple functions in flavonoids. We establish a structure-activity relationship of flavonoids that should be useful for designing chemical reagents with multiple reactivities against the pathological factors of AD.

SUBMITTER: Nam G

PROVIDER: S-EPMC8162271 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Evaluation of a flavonoids library for inhibition of pancreatic ?-amylase towards a structure-activity relationship.

Project description:?-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit ?-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an -OH group at 3'- and 4'- positions of B-ring and at 5- and 7- positions of A-ring and the C2?=?C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of ?-amylase and may be considered as possible alternatives to the modulation of T2DM.

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| S-EPMC7525318 | biostudies-literature

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| S-EPMC6829050 | biostudies-literature

Improved quantitative structure-activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems.

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| S-EPMC7088272 | biostudies-literature

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