Date of Completion

7-2021

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Molecular Docking Simulation, Alzheimer Disease

Abstract

Asparagine endopeptidase is responsible for the direct cleavage of tau protein that turns into toxic neurofibrillary tangles in the brain tissue, which then leads to a neurodegenerative ailment called Alzheimer’s disease. A study suggests that there are molecules present in Vigna radiata sprouts that can inhibit asparagine endopeptidase. However, the bioactive compounds have not been identified. In this study, phenolic compounds found in Vigna radiata sprouts were docked against asparagine endopeptidase using Autodock Vina to examine their capability for binding. Five compounds with the most negative binding energies were selected for bioavailability testing using SwissADME and toxicity testing using PASS Online and were compared to a xanthine derivative that was synthesized specifically as an inhibitor for asparagine endopeptidase. After this, the selected compounds were derivatized to improve their binding energies, increase their bioavailability and decrease their neurotoxic properties. The selected secondary metabolites which include isovitexin-6-O”-glucoside, pelagornidin-3,6-malonylglucoside, isovitexin, chlorogenic acid and pelagornidin-3-glucoside had more negative binding energies compared to the xanthine derivative reference compound. The derivatives, dehydroxyisovitexin-6-O”-glucoside, dehydroxypelagornidin-3,6-malonylglucoside and dehydroxypelagornidin-3-glucoside, showed better binding energies. Initially, all the metabolites, except for the dehydroxyisovitexin derivative, had unacceptable bioavailability scores but after derivatization, all the molecules had acceptable bioavailability scores. All the metabolites were initially neurotoxic, and derivatization has succeeded in eliminating potential neurotoxic side effects.

First Advisor

Margel C. Bonifacio

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