N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells
<p>Formaldehyde is a pollutant and human metabolite that is toxic at high concentrations. Biological studies on formaldehyde are hindered by its high reactivity and volatility, which make it challenging to deliver quantitatively to cells. Here, we describe the development and validation of a s...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Royal Society of Chemistry
2023
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| _version_ | 1797111793196204032 |
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| author | Emms, VL Lewis, LA Beja, L Bulman, NFA Pires, E Muskett, FW Mccullagh, JSO Swift, LP McHugh, PJ Hopkinson, RJ |
| author_facet | Emms, VL Lewis, LA Beja, L Bulman, NFA Pires, E Muskett, FW Mccullagh, JSO Swift, LP McHugh, PJ Hopkinson, RJ |
| author_sort | Emms, VL |
| collection | OXFORD |
| description | <p>Formaldehyde is a pollutant and human metabolite that is toxic at high concentrations. Biological studies on formaldehyde are hindered by its high reactivity and volatility, which make it challenging to deliver quantitatively to cells. Here, we describe the development and validation of a set of <em>N</em>-acyloxymethyl-phthalimides as cell-relevant formaldehyde delivery agents. These esterase-sensitive compounds were similarly or less inhibitory to human cancer cell growth than free formaldehyde but the lead compound increased intracellular formaldehyde concentrations, increased cellular levels of thymidine derivatives (implying increased formaldehyde-mediated carbon metabolism), induced formation of cellular DNA-protein cross-links and induced cell death in pancreatic cancer cells. Overall, our <em>N</em>-acyloxymethyl-phthalimides and control compounds provide an accessible and broadly applicable chemical toolkit for formaldehyde biological research and have potential as cancer therapeutics.</p> |
| first_indexed | 2024-03-07T08:15:22Z |
| format | Journal article |
| id | oxford-uuid:3d9d7cf5-b746-4141-b07b-f8fa5e45a31f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:15:22Z |
| publishDate | 2023 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:3d9d7cf5-b746-4141-b07b-f8fa5e45a31f2023-12-22T07:35:46ZN-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d9d7cf5-b746-4141-b07b-f8fa5e45a31fEnglishSymplectic ElementsRoyal Society of Chemistry2023Emms, VLLewis, LABeja, LBulman, NFAPires, EMuskett, FWMccullagh, JSOSwift, LPMcHugh, PJHopkinson, RJ<p>Formaldehyde is a pollutant and human metabolite that is toxic at high concentrations. Biological studies on formaldehyde are hindered by its high reactivity and volatility, which make it challenging to deliver quantitatively to cells. Here, we describe the development and validation of a set of <em>N</em>-acyloxymethyl-phthalimides as cell-relevant formaldehyde delivery agents. These esterase-sensitive compounds were similarly or less inhibitory to human cancer cell growth than free formaldehyde but the lead compound increased intracellular formaldehyde concentrations, increased cellular levels of thymidine derivatives (implying increased formaldehyde-mediated carbon metabolism), induced formation of cellular DNA-protein cross-links and induced cell death in pancreatic cancer cells. Overall, our <em>N</em>-acyloxymethyl-phthalimides and control compounds provide an accessible and broadly applicable chemical toolkit for formaldehyde biological research and have potential as cancer therapeutics.</p> |
| spellingShingle | Emms, VL Lewis, LA Beja, L Bulman, NFA Pires, E Muskett, FW Mccullagh, JSO Swift, LP McHugh, PJ Hopkinson, RJ N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title | N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title_full | N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title_fullStr | N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title_full_unstemmed | N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title_short | N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells |
| title_sort | n acyloxymethyl phthalimides deliver genotoxic formaldehyde to human cells |
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