Date of Submission
Spring 2024
Academic Program
Chemistry and Biochemistry
Project Advisor 1
Swapan Jain
Abstract/Artist's Statement
Ru79 and Cu65 represent promising candidates for novel inorganic anticancer treatments, featuring Ruthenium (II) or Copper (II) metal centers. These compounds incorporate metformin and phenformin, potentially enhancing therapeutic efficacy compared to existing anticancer agents. Prior research on Ruthenium-based compounds has elucidated their interactions with DNA and RNA [1]. Notably, DHFR mRNA emerges as a significant molecular target due to RNA's chemical similarity to DNA and its essential role in cellular processes. Another key target for this project is the DHFR enzyme due to its crucial role in cellular function and regeneration
Cancer research has extensively focused on the folic acid pathway, wherein dihydrofolate reductase (DHFR) catalyzes the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), utilizing NADPH as a cofactor for the biosynthesis of purines, thymidylate, and various amino acids [2]. Specifically, our investigation centers on the binding affinity of ruthenium complexes with the DHFR enzyme. We aimed to answer whether phenformin and metformin-based compounds influence DHFR binding and catalytic activity.
Our study employed in vitro assays to assess the binding affinity of Phenformin, Metformin, Ru79, Cu65, and Ru-cymene with the DHFR enzyme. Methodologies encompassed seed cultures, plasmid extraction, restriction digestion, isoamyl:phenol:chloroform purification, transcription, incubation with metal complexes, translation, DHFR activity assays, gel electrophoresis, EMSA gel studies, and fluorescence quenching studies. Results indicate significant potential for phenformin and metformin-based drugs to inhibit DHFR enzymatic activity effectively, offering promise as future anticancer therapies.
Open Access Agreement
On-Campus only
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Recommended Citation
Saccomanno, Sage Martina, "Interactions of Ruthenium(II) and Copper(II) Metal Complexes with DHFR: Inhibitory Effects on Enzyme Activity and RNA Binding" (2024). Senior Projects Spring 2024. 256.
https://digitalcommons.bard.edu/senproj_s2024/256
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