Fall 2023/Spring 2024 Biochemistry Seniors and their Research

Leah Biwot,   Advisor: Dr. S. Tartakoff
Synthesis and Study of Acridine Derivatives as Potential Chemotherapeutic Agents

Acridine dyes are commonly used for DNA-drug interaction studies because their polycyclic, planar, and aromatic structures can intercalate between adjacent DNA bases, stopping transcription and serving as potential chemotherapeutic agents. In my research, I have prepared a number of acridine derivatives to better understand DNA-ligand interactions and structure-activity relationships. These derivatives were prepared using two approaches: (1) by directly modifying proflavine with various reactions (e.g., amine acylation and aromatic substitution) and (2) by using the Ullman-Goldberg cross-coupling reaction to build up the acridine core, which allows for the introduction of more substituents via later nucleophilic substitution of the resultant 9-chloroacridines. I have also investigated the methylation of the aromatic acridine nitrogen to render the resulting products water-soluble and facilitate binding studies with DNA via a range of techniques, including melting point, viscosity, circular dichroism (CD), and kinetics. These studies will provide insight into how various functional groups affect the binding modes and intercalation properties of acridine derivatives

 

Maddy Ruggiera,  Advisor: Dr. S. Tartakoff
Synthesis of Novel Proflavine Derivatives as Possible DNA Binding Agents

Organic synthesis gives pharmaceutical chemists the ability to create complex molecules from cheap and readily available chemical compounds. Many of these complex organic molecules are bioactive molecules that can function as DNA intercalators— molecules that bind to DNA in a variety of modes, causing a change in the DNA. This change oftentimes results in a halt in cell function or cell death, making intercalating molecules promising chemotherapeutic agents. This project centers around creating derivatives from a known intercalating molecule, proflavine, in order to create DNA intercalators that are more soluble in water and more electrophilic, allowing for proflavine’s daughter-molecules to more effectively bind to DNA. While utilizing literature and known reactions, a small library of proflavine derivatives is being created based on the condensation of functional groups onto proflavine’s unsubstituted amines, as well as rebuilding the core acridine structure of proflavine to include reactive groups on the aromatic rings. The goal of this project is the creation of both known and novel proflavine derivatives for use in DNA and kinetics studies.