Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Parkinson’s disease, asparagine endopeptidase, mangostin

Abstract

Parkinson’s disease is a neurodegenerative disorder that has no known cure up to date. It is characterized by progressive impairment of motor control that mainly affects the brain. The asparagine endopeptidase or AEP is activated in people with Parkinson’s disease, which causes unwanted symptoms that can make the illness severe. Mangostin compounds, which include αmangostin, β-mangostin, γ-mangostin, and 1-isomangostin, found in the pericarp of mangosteen were chosen to be studied due to their promising biological activities in the body and the presence of a higher concentration of these compounds as compared with the other parts of the fruit. These mangostin compounds were docked against AEP to check their affinity towards the enzyme. The results showed that α-mangostin and β-mangostin have a binding score of -5.3 kcal/mol, while γ-mangostin and 1-isomangostin have binding scores of -5.4 kcal/mol and -5.6 kcal/mol, respectively. The binding scores are not negative enough to have a good affinity towards AEP. Aside from these parent compounds, Levodopa, which is a drug prescribed to patients with Parkinson’s disease, was chosen to be the reference compound. Upon docking it against AEP, it was shown to have a binding score of -5.1 kcal/mol. Therefore, in order to improve the binding affinities of the mangostin parent compounds and produce compounds which have higher affinities towards AEP when compared to Levodopa, mangostin derivatives were designed, docked, and their lowest possible binding energies were determined. The top derivative, aminooxane derivative of γ-mangostin, has a binding energy of -7.3 kcal/mol while the top two and three derivatives, namely, 3-aminopropanol derivative of 1-isomangostin, and diaminooxane derivative of α-mangostin, have a binding score of -7.2 kcal/mol. Lastly, the top four and five derivatives, fluoroaminooxane derivative of γ-mangostin, and fluorodiamine derivative of β-mangostin, have binding energies of -7.1 kcal/mol and -7.0 kcal/mol, respectively. The possible ADMET properties of these derivatives were determined through different softwares. The results showed that the said derivatives are presumed to have better efficacy when used as components of a drug. Two of them, namely the aminooxane derivative of γmangostin and the 3-aminopropanol derivative of 1-isomangostin, are observed to be more permeable to both the BBB and GI as compared to the reference compound Levodopa and can be used for oral intake. Their toxicity values, on the other hand, are within the normal range or do not exhibit any toxicity, therefore they are probably non-toxic, indicating that these derivatives are possibly much safer for human use.

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