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

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2024-09-24 DOI:10.1002/cmdc.202400536

Zachary C Brandeburg, Sakariyau A Waheed, Carina A Derewonko, Caroline E Dunn, Ethan C Pfeiffer, Ann Marie E Flusche, Robert J Sheaff, Angus A Lamar

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引用次数: 0

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-h 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-h 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 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.

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作为胰腺癌细胞线粒体 ATP 生成代谢抑制剂的 N-(1H-吲哚-6-基甲基)苯磺酰胺类似物的合成与生物学评价。

我们合成了一个由 26 种吲哚基磺酰胺类化合物和 12 种基于 6-吲哚基框架的酰胺和酯类类似物组成的化合物库，旨在靶向治疗胰腺癌。吲哚基磺酰胺化合物的细胞毒性是通过传统的（48 小时化合物暴露）试验，针对 7 种胰腺癌细胞系和 1 种非癌细胞系进行测定的。我们还利用实验室开发的快速筛选（化合物暴露 2 小时）试验评估了这些化合物作为 ATP 生成代谢抑制剂的潜在作用。使用快速测定法确定了活性化合物的 IC50 值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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