Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Alzheimer’s Disease

Abstract

δ-Secretase enzyme facilitates the progression of Alzheimer's disease (AD) by its contribution to the accumulation of beta-amyloid plaques and hyperphosphorylation of tau. Secondary metabolites present in plants have been found to have pharmacological effects that treat several diseases and disorders. For this study, 79 secondary metabolites were obtained from Coriandrum sativum (C. sativum) and docked with the enzyme. Three secondary metabolites with the highest negative binding energy were apigenin-7-O-glucuronide with -7.7 kcal/mol, chlorogenic acid with -7.0 kcal/mol, and isoquercitrin with -6.8 kcal/mol. The common amino acids that the ligands interacted to was Tyr41, Arg44, and Tyr228. Less interactions are present between the reference compounds and enzyme compared with the secondary metabolites. Hence, the top 3 ligands did not pass through the BBB which means it that was not orally bioavailable due to the number of polar groups present in the chosen ligands. Further derivatization of the ligands is needed to improve its characteristics since it also possessed toxic adverse effects including neurotoxicity. Dehydroxy-derived ligands of the parent compounds were made which improved the primary results. The best drug candidate is dihydroxy-hydro-methyl-chlorogenic acid derivative with a binding affinity of -7.0 kcal/mol with a negative P-gp substrate and having to penetrate the BBB. Other derived ligands that were not able to pass the BBB and with toxic adverse effects got eliminated.

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