Development of Molecule to Replace Monoclonal Antibodies used for the Prevention of Abdominal Fistulas

Marah Susko

Abstract

Crohn's disease, a form of Chronic Inflammatory Bowel disease, primarily affects the lining of the digestive tract and is highly complex. The current hypothesis is that it is autoimmune-related, and treatment mainly pertains to controlling symptoms. One common symptom is intestinal fistulas caused by ulcers or sores tunneling through the abdomen and areas surrounding the anus/rectum. Currently fistulas are treated using surgery. The only preventative medications for abdominal fistulas are intravenous injections of monoclonal antibodies targeting inflammation through the TNF-α cytokine. The problem with these monoclonal antibodies is they must be administered intravenously every eight weeks. This is not always a viable option. My goal was to create an orally viable medication which can target TNF-α. I chose curcumin as a lead molecule and used molecular editing software Avogadro to create modifications to the drug lead molecule. I knew I needed a lead molecule to work off as orally viable medication must consist of small molecules. Thus, I chose curcumin as a drug lead, as it is what causes the anti-inflammatory properties in turmeric through binding to the TNF-α cytokine. I made six modifications to the original structure of curcumin, then further combining the modification to create several more. Modification 05 produced the best results. The change in Modification 05 is the change of an ethyl group to a trifluoro ethyl group; I replaced the hydrogens in this group with fluorine. Future experimentation will be needed to determine whether the novel molecule prevents fistulas, specificity to TNF-α, and adverse effects.

 
Apr 2nd, 9:30 AM

Development of Molecule to Replace Monoclonal Antibodies used for the Prevention of Abdominal Fistulas

HSS 203

Crohn's disease, a form of Chronic Inflammatory Bowel disease, primarily affects the lining of the digestive tract and is highly complex. The current hypothesis is that it is autoimmune-related, and treatment mainly pertains to controlling symptoms. One common symptom is intestinal fistulas caused by ulcers or sores tunneling through the abdomen and areas surrounding the anus/rectum. Currently fistulas are treated using surgery. The only preventative medications for abdominal fistulas are intravenous injections of monoclonal antibodies targeting inflammation through the TNF-α cytokine. The problem with these monoclonal antibodies is they must be administered intravenously every eight weeks. This is not always a viable option. My goal was to create an orally viable medication which can target TNF-α. I chose curcumin as a lead molecule and used molecular editing software Avogadro to create modifications to the drug lead molecule. I knew I needed a lead molecule to work off as orally viable medication must consist of small molecules. Thus, I chose curcumin as a drug lead, as it is what causes the anti-inflammatory properties in turmeric through binding to the TNF-α cytokine. I made six modifications to the original structure of curcumin, then further combining the modification to create several more. Modification 05 produced the best results. The change in Modification 05 is the change of an ethyl group to a trifluoro ethyl group; I replaced the hydrogens in this group with fluorine. Future experimentation will be needed to determine whether the novel molecule prevents fistulas, specificity to TNF-α, and adverse effects.