Date of Completion

2023

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Aromatase, lignans, breast cancer, molecular docking

Abstract

Aromatase is part of the cytochrome P450 superfamily and synthesizes estrogens and is abnormally expressed within the breast cancer cells. Among therapies employed in cancer treatment is the utilization of natural products, including phytoestrogens such as lignans. Out of twenty-seven lignans docked against aromatase, the five with the most negative binding energies had their interactions with the enzyme visualized and their ADMET properties predicted. The top-ranked lignans obtained more negative binding energies than letrozole and their ADME properties were consistent with the accepted values. Toxicity showed some deviation from the standard drug. Upon modification, unfavorable interactions were addressed and the lignans still presented more negative binding energies compared to letrozole. ADME properties showed only one deviation from the rule of 5 out of all the modifications but there were some deviations for GI absorption and BBB permeability while varying results were presented in the immunotoxicity endpoint with the first modifications of both sesamoid and sesamin being the only ones similar to that of the standard drug, letrozole. Saturation can also be an emphasis for this modification in order to contribute to an optimal ADMET. Recommendations include further modifications to be performed utilizing other phytoestrogen groups not used in the study. The study can also be used as a starting point or reference in conducting research on other beneficial effects in free radicals or in immune response. Lastly, performing in vitro and in vivo studies using lignans is also recommended to have a further understanding on its inhibitory properties through observations of responses with actual subjects.

First Advisor

Tabitha L. Amora

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