Date of Completion

2023

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Colored rice anthocyanins, Colon Cancer. Cancer management, Molecular Docking, Bioavailability, Toxicity

Abstract

There are several proteins that impacts the way colon cancer tumor cells proliferate. Anthocyanins are compounds that naturally occurs in dark pigmented crops such as colored rice. This study investigates the potential of colored rice anthocyanins such as cyanidin, malvidin, peonidin, pelargonidin, and their known derivatives in the inhibition of colon cancer proliferation. Four colon cancer-related proteins and thirteen colored rice anthocyanins were used as targets and ligands in the docking study in order to assess which anthocyanins were able to bind best to proteins. Analysis showed that the anthocyanin that was able to bind best to multiple proteins that is thymidylate synthase and rearranged during transfection receptor tyrosine kinase (RETK), was cyanidin 3-O rutinoside hence, making it the top inhibitor for the study. This is in comparison to the binding affinities for the reference drugs used for each protein which are -7.5 kcal/mol for fluorodeoxyuridine monophosphate (FdUMP), the reference drug for thymidylate synthase, and - 8.8 for regorafenib, the reference drug for RETK. The binding affinity of cyanidin 3-O rutinoside for each protein are -9.2 kcal/mol and -8.6 kcal/mol respectively. Second to it was peonidin 3-(6''-

p-coumaroyl-glucoside) 5-glucoside which was able to bind to two proteins, thymidylate synthase and RETK, as well. However, the difference for the binding affinities recorded for peonidin 3-(6''- p-coumaroyl-glucoside) 5-glucoside was smaller than that of the top inhibitor. The binding affinity of peonidin 3-(6''-p-coumaroyl-glucoside) 5-glucoside are -10.5 kcal/mol and -8.8 kcal/mol respectively. The third and fourth top anthocyanins for the study are cyanidin 3,5-O diglucoside and cyanidin 3-O glucoside. Both of these anthocyanins were able to exhibit a better binding affinity than the reference drug to at least one protein. Cyanidin 3,5-O diglucoside has a binding affinity of -9.0 kcal/mol for thymidylate synthase, while cyanidin 3-O glucoside has a binding affinity of -8.9 kcal/mol for RETK. Lastly, for the absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis shows that these top four anthocyanins all exhibit a low oral bioavailability but low toxicity. With this, molecular dynamics simulation for the confirmation of docking results and derivatization for the compounds was recommended to improve absorption, distribution, metabolism, and excretion (ADME) properties of the colored rice anthocyanins employed in this study.

First Advisor

Margel C. Bonifacio

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