VCOM Louisiana Research Day Program Book 2024

physicochemical properties, lipophilicity, and overall drug-likeness. Finally, our continuous research includes employing Western blot analyses for detecting alterations in protein expression and conducting cell cycle analysis through flow cytometry to assess the impact of our compound on various stages of the cell cycle. Results: Our lab successfully developed microwave-assisted Suzuki-coupling reactions, leading to the synthesis of a diverse array of 25 small-molecule compounds. Subsequently, we confirmed the structure of each compound using NMR and HRMS analyses. Following this, we initiated the screening of our compounds against CRC cancer cells (HCT-116 and Widr) using the MTT assay. According to our screening results, we identified 8 highly potent and active compounds, with particular emphasis on SML 167 and SML-172. Notably, SML-172 exhibited superior selectivity compared to SML-167. Additionally, we performed molecular docking for our compounds and their analogs, targeting the protein structures of TTK and AuroraKB. Our results demonstrated a robust binding affinity of our compounds to these proteins, with binding energies ranging from -8 to -10 kcal/mol. Furthermore, the most potent compound, SML 172, showed considerable colony formation inhibitory potential and anti-metastatic potential which we confirmed through colony formation and wound healing assays. Additionally, we conducted a western blot analysis to examine the effect of our selective compound on the alteration of targeted proteins. The western blot results revealed that our compound effectively decreased the expression of the targeted

proteins. Finally, we are currently working on evaluating the impact of SML-172 on different stages of the cell cycle using flow cytometry. Conclusions: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Recognizing the limitations of current treatments, we aimed to develop small-molecule compounds targeting Protein Tyrosine Kinases (PTKs), specifically TTK and Aurora kinase B, implicated in CRC initiation and progression. Our successful synthesis of 25 diverse small-molecule compounds via microwave-assisted Suzuki-coupling reactions. Notably, our screening efforts against CRC cancer cells identified eight potent compounds, with SML-172 demonstrating superior selectivity. Molecular docking studies reinforced our findings, revealing robust binding affinities of the compounds to TTK and AuroraKB proteins. potential and anti-metastatic activity through colony formation and wound healing assays. Western blot analyses demonstrated its efficacy in decreasing the expression of targeted proteins associated with cancer progression. These results, coupled with ongoing evaluations of SML-172’s impact on different cell cycle stages using flow cytometry, underscore the compound’s potential as a targeted therapeutic agent. Our comprehensive approach, from synthesis to functional assays and molecular investigations, positions SML-172 as a compelling candidate for in vivo characterization as the next phase of the study. Further exploration of SML-172 showed considerable colony formation inhibitory

37 2024 Via Research Recognition Day