Synthesis and Biological Evaluation of N-(1H-Indol-6-ylmethyl)benzenesulfonamide Analogs as Metabolic Inhibitors of Mitochondrial ATP Production in Pancreatic Cancer Cells.

Abstract

A library of 26 indolyl sulfonamides and 12 amide and ester analogs based upon the 6-indolyl framework has been synthesized in an effort to target pancreatic cancer. The cytotoxicity of the indolyl sulfonamide compounds has been determined using a traditional (48-hour compound exposure) assay against 7 pancreatic cancer cell lines and 1 non-cancerous cell line. The potential role of the compounds as metabolic inhibitors of ATP production was evaluated using a rapid screening (2-hour compound exposure) assay developed within our laboratories. The IC50 values of the active compounds were determined using the rapid assay and six compounds displayed an IC50 value <5 μM against one or more pancreatic cancer cell lines. The ester analogs also display significant activity as potential metabolic inhibitors of ATP production with four of the six compounds displaying an IC50 value <5 μM against one or more pancreatic cancer cell lines.