Carmofur Analogs for In Vitro Evaluation Against Cancer Cells and SARS-CoV-2 Main Protease

July 2, 2024 Colloquia
Department of Chemistry, Biochemistry & Physics
Design and Synthesis of Novel Carmofur Analogs for In Vitro Evaluation Against Cancer Cells and the SARS-CoV-2 Main Protease
During COVID-19, carmofur, a 5-fluorouracil derivative initially developed as an antineoplastic agent against colorectal cancer, was identified through a high-throughput drug repurposing screen as a potent covalent inhibitor of the SARS-CoV-2 main protease (Mpro). Thus, it is a promising therapeutic candidate against COVID-19. Utilizing 19F NMR to quantitatively track reaction rates in various reaction conditions, our group optimized the synthesis of carmofur and synthesized eleven novel carmofur analogs aimed at exploring the impact of structural modification on biological activity. To evaluate the efficacy of our compounds in vitro, we performed MTT assays on various cancer cell lines to probe their anti-proliferative activity and a colorimetric assay to assess our analogs’ inhibition of Mpro. We found that certain analogs ourperformed carmofur in their antiproliferative activity and inhibition of Mpro.
RESEARCHERS: Eileen Z., Amador Valley High School ‘25
ADVISOR: Njoo Lab Synthesis | Physical Organic Chemistry | Catalysis | Chemical Biology | Spectroscopy | Medicinal Chemistry
KEYWORDS: Quantum Computing | Brain Tumors | Machine Learning| Mathematical Morphological Reconstruction | Convolutional Neural Networks