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

Abstract

AbstractIn 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.