Name: Raghav Tripathi High School: Westview High School Mentor: Dr. Iwao Ojima

1. Name: Raghav Tripathi High School: Westview High School Mentor: Dr. Iwao Ojima Project Title: Design and Synthesis of Novel Fatty Acid Binding Protein Inhibitors for Analgesic and Anti-Inflammatory Effects through Increases in Endogenous Anandamide Concentrations Over 1.5 billion people worldwide suffer from chronic pain, a detriment to worker productivity, quality of life, etc. Furthermore, excess acute pain afflicts billions worldwide. Recently, preclinical studies have indicated that elevated levels of the endocannabinoid “anandamide” (AEA) result in beneficial pharmacological effects on pain, stress, and inflammation, and may ameliorate drug withdrawal effects without unintended side-effects. Fatty acid binding proteins (FABPs) are intracellular transporters for AEA. As such, FABPs provide targets for inhibition by small molecules to increase endogenous AEA levels due to their tissue specificity and AEA transport mechanism. This study developed innovative compounds for FABP inhibition. First, 1,057,042 molecules were virtually screened for binding affinity to FABP using a computational analysis program (DOCK). Then, 48 compounds with the greatest modeled efficacy were screened in vitro, and the compound with the greatest FABP inhibition (truxillic acid) was synthesized and assayed against HeLa cells. Results indicate that truxillic acid significantly inhibits the cellular uptake of AEA. For further drug optimization, libraries of truxillic acid functional group modifications were chemically synthesized and “DOCKed.” The results strongly support the potential of these novel small molecules for FABP inhibition. The synthesized compounds may contribute to the next generation of innovative analgesic medications.