Expansion of a Synthesized Library of N-Benzyl Sulfonamides Derived from an Indole Core to Target Pancreatic Cancer

In an effort to further investigate previously observed activity of indolyl sulfonamides towards pancreatic cancer cell lines, a library of 44 compounds has been synthesized. The biological activity of the compounds has been determined using two different screening assay techniques against 7 pancreatic cancer cell lines and 9 non-pancreatic cancer cell lines. In the first assay, the cytotoxicity of the compounds was evaluated using a traditional (48 hour compound exposure) method. An in silico investigation was conducted to determine if the compounds might be inducing cell death by inhibiting the S100A2-p53 protein-protein interaction. In the second assay, the potential role of the compounds as metabolic inhibitors of ATP production was evaluated using a rapid screening (1–2 hour compound exposure) method. IC₅₀ values of the hit compounds were obtained and four compounds displayed sub-micromolar potency against PANC-1 cells. The investigation has provided several compounds that display selective in vitro activity toward pancreatic cancer that warrant further development.