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Expansion of a Synthesized Library of N-Benzyl Sulfonamides Derived from an Indole Core to Target Pancreatic Cancer
Megan D Hopkins1, Ian J Costello1, Zachary C Brandeburg1
1Department of Chemistry and Biochemistry, The University of Tulsa, 800 South Tucker Drive, 74104, Tulsa, OK, USA.
Abstract:
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.
Insights
Researchers synthesized 44 indolyl sulfonamides to study their effects on pancreatic cancer. Four compounds showed potent activity against PANC-1 cells, indicating potential for new pancreatic cancer treatments.
Area of Science:
- Medicinal Chemistry
- Oncology
- Molecular Biology
Background:
- Indolyl sulfonamides have shown prior activity against pancreatic cancer cell lines.
- Pancreatic cancer remains a significant health challenge with limited effective treatments.
Purpose of the Study:
- To synthesize and evaluate a library of indolyl sulfonamides for anticancer activity.
- To investigate the mechanism of action, including cytotoxicity and metabolic inhibition.
- To identify selective compounds for pancreatic cancer treatment.
Main Methods:
- Synthesis of 44 indolyl sulfonamide compounds.
- Cytotoxicity screening against 7 pancreatic and 9 non-pancreatic cancer cell lines (48-hour exposure).
- In silico analysis of S100A2-p53 protein-protein interaction inhibition.
- ATP production metabolic inhibition assay (1-2 hour exposure).
Main Results:
- Four indolyl sulfonamides demonstrated sub-micromolar potency against PANC-1 cells.
- Compounds were evaluated for cytotoxicity and metabolic inhibition of ATP production.
- Selective in vitro activity against pancreatic cancer cell lines was observed.
Conclusions:
- The study identified several indolyl sulfonamide derivatives with promising selective in vitro activity against pancreatic cancer.
- These compounds warrant further investigation as potential therapeutic agents for pancreatic cancer.
