Products Cited in Publications Worldwide Inhibition of ATP Production in Pancreatic Cancer Cells by a Library of N‐(1H‐Indol‐4‐ylmethyl) benzenesulfonamide and N‐(1H‐Indol‐5‐ylmethyl) benzenesulfonamide Analogs

Inhibition of ATP Production in Pancreatic Cancer Cells by a Library of N‐(1H‐Indol‐4‐ylmethyl) benzenesulfonamide and N‐(1H‐Indol‐5‐ylmethyl) benzenesulfonamide Analogs

Witt, Ryan C; Dunn, Caroline E; Zanders, Levi A; Edema, Adeleye A; Waheed, Sakariyau A; Derewonko, Carina A; Franzen, Lauren C; Osborn, Presley L; Caudle, Jenna D; Sheaff, Robert J

DOI: PMID:

Abstract

A library of 50 indolyl sulfonamides and 9 amide analogs based upon the 4-indolyl and 5-indolyl frameworks has been synthesized to target the metabolic processes of pancreatic cancer. Thirteen of the 50 compounds were identified as cytotoxic at 50 μM 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 then evaluated using a rapid screening (1-2 hour compound exposure) assay developed within our laboratories. The rapid assay identified 10 compounds as strong or moderate hits at 3 μM against the panel of pancreatic and non-cancerous cell lines. The IC50 values of the active compounds were determined using the rapid assay in the absence of glucose and four of the compounds displayed an IC50 value <1 μM against one or more pancreatic cancer cell lines. Comparison of IC50 values of the active compounds in the presence of glucose implicates the potential role of the compounds as oxidative phosphorylation (OXPHOS) inhibitors of ATP production. Lastly, a series of amide analogs were synthesized and screened for activity to determine the structural importance of the sulfonamide functionality.

Keywords

Indole ; oxidative phosphorylation inhibitor ; OXPHOS inhibitor ; pancreatic cancer ; chemotherapy resistance

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A11531581881-74-595%

(1H-Indol-5-yl)methanamine

143.0/10g

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4-Aminomethylindole

A1931033468-18-695%

4-Aminomethylindole

640.0/25g

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