Targeting mitochondrial ATP production of glioblastoma using sulfonamide and amide analogs of amantadine and memantine as metabolic inhibitors
Year: 2025
Type: article
Abstract: A library of 67 analogs of amantadine and memantine has been synthesized and screened for activity against 4 mammalian cell lines, including U-87 (glioblastoma). The library was screened using both a traditional cytotoxicity assay and a rapid assay to detect activity as metabolic inhibitors of ATP production. Two protocols were employed to identify activity targeting mitochondrial ATP (TCA cell cycle) production. In Protocol A (DMEM media +2-DG), 16 compounds were identified as strong hits against U-87 cells at 50 μM. Using Protocol B (L-15 media), 10 compounds were identified as strong hits at 12.5 μM against U-87 cells. Several compounds were identified as hits toward U-87 cells using the rapid assay that were not identified using the traditional cytotoxicity assay. The IC 50 values of the hits against U-87 cells were determined against U-87 and non-cancerous HDF cells. The investigation has resulted in the identification of several compounds with the predicted ability to cross the blood-brain barrier that display high potency (0.82 μM for compound 20 ) and selectivity (selectivity index value ≥7 for compound 24 ) toward U-87 cells. 2009 Elsevier Ltd. All rights reserved.
Source: Results in Chemistry
Institution: University of Tulsa
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,870
OpenAlex ID: W4408148089