Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Coprinopsis lagopus, ergosterol, molecular docking, Ubc13

Abstract

Breast cancer is a serious societal concern, particularly among women worldwide. Various treatments, such as chemotherapy, are now applied, but the search for a more potent and safer treatment continues. Consequently, the evaluation of compounds extracted from a mushroom species that can be found in the Philippines - Coprinopsis lagopus, is conducted using in silico methods. Through molecular docking with Ubc13, both ergosterol and 22-dihydroergosterol achieved high binding scores with Ubc13. Ergosterol, which had a binding score of -6.6 kcal/mol close to the reference drug neratinib which had a binding score of -6.8 kcal/mol, was further derivatized to obtain higher binding scores. The physicochemical features of ergosterol were modified throughout the design. The top five derivatives were produced, with binding energy scores of -8.7 kcal/mol for the first two and -8.6 kcal/mol, -8.5 kcal/mol, and -8.4 kcal/mol for the remaining derivatives. The concerns to address among the made derivatives were their high molecular weight and slightly high lipophilicity. Analysis of ergosterol derivatives' toxicity revealed that all are unlikely to induce adverse effects on the human body. Hence, the top 5 derivatives are potential drug candidates to treat breast cancer. Considering that the results of SwissADME and PASS Online of the top 5 derivatives are almost similar, 444679-D1 is considered the best compound as it had the most negative binding energy. The noteworthy findings of this study suggest that the designed compounds can be analyzed and optimized using molecular dynamics, in vivo, and in vitro techniques in order to determine their capacity to inhibit the enzyme and be used as a candidate for therapeutic development.

First Advisor

Margel C. Bonifacio

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