Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position
A series of 3-(benzyl-substituted)-imidazo[5,1-d]-1,2,3,5-tetrazines (13) and related derivatives with 3-heteromethyl groups has been synthesised and screened for growth-inhibitory activity in vitro against two pairs of glioma cell lines with temozolomide-sensitive and -resistant phenotypes dependen...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Royal Society of Chemistry
2018
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| Online Access: | https://eprints.nottingham.ac.uk/49226/ |
| _version_ | 1848797949809655808 |
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| author | Cousin, David Hummersone, Marc Bradshaw, Tracey D. Zhang, Jihong Moody, Christopher J. Foreiter, Magdalena Summers, Helen Lewis, William Wheelhouse, R.T. Stevens, Malcolm F.G. |
| author_facet | Cousin, David Hummersone, Marc Bradshaw, Tracey D. Zhang, Jihong Moody, Christopher J. Foreiter, Magdalena Summers, Helen Lewis, William Wheelhouse, R.T. Stevens, Malcolm F.G. |
| author_sort | Cousin, David |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | A series of 3-(benzyl-substituted)-imidazo[5,1-d]-1,2,3,5-tetrazines (13) and related derivatives with 3-heteromethyl groups has been synthesised and screened for growth-inhibitory activity in vitro against two pairs of glioma cell lines with temozolomide-sensitive and -resistant phenotypes dependent on the absence/presence of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In general the compounds had low inhibitory activity with GI50 values > 50 μM against both sets of cell lines. Two silicon-containing derivatives, the TMS-methylimidazotetrazine (9) and the SEM-analogue (10), showed interesting differences: compound (9) had a profile very similar to that of temozolomide with the MGMT+ cell lines being 5 to 10-fold more resistant than MGMT– isogenic partners; the SEM-substituted compound (10) showed potency across all cell lines irrespective of their MGMT status. |
| first_indexed | 2025-11-14T20:12:00Z |
| format | Article |
| id | nottingham-49226 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:12:00Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-492262020-05-04T19:27:19Z https://eprints.nottingham.ac.uk/49226/ Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position Cousin, David Hummersone, Marc Bradshaw, Tracey D. Zhang, Jihong Moody, Christopher J. Foreiter, Magdalena Summers, Helen Lewis, William Wheelhouse, R.T. Stevens, Malcolm F.G. A series of 3-(benzyl-substituted)-imidazo[5,1-d]-1,2,3,5-tetrazines (13) and related derivatives with 3-heteromethyl groups has been synthesised and screened for growth-inhibitory activity in vitro against two pairs of glioma cell lines with temozolomide-sensitive and -resistant phenotypes dependent on the absence/presence of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In general the compounds had low inhibitory activity with GI50 values > 50 μM against both sets of cell lines. Two silicon-containing derivatives, the TMS-methylimidazotetrazine (9) and the SEM-analogue (10), showed interesting differences: compound (9) had a profile very similar to that of temozolomide with the MGMT+ cell lines being 5 to 10-fold more resistant than MGMT– isogenic partners; the SEM-substituted compound (10) showed potency across all cell lines irrespective of their MGMT status. Royal Society of Chemistry 2018-01-19 Article PeerReviewed Cousin, David, Hummersone, Marc, Bradshaw, Tracey D., Zhang, Jihong, Moody, Christopher J., Foreiter, Magdalena, Summers, Helen, Lewis, William, Wheelhouse, R.T. and Stevens, Malcolm F.G. (2018) Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position. MedChemComm . ISSN 2040-2503 http://pubs.rsc.org/en/content/articlepdf/2018/md/c7md00554g doi:10.1039/C7MD00554G doi:10.1039/C7MD00554G |
| spellingShingle | Cousin, David Hummersone, Marc Bradshaw, Tracey D. Zhang, Jihong Moody, Christopher J. Foreiter, Magdalena Summers, Helen Lewis, William Wheelhouse, R.T. Stevens, Malcolm F.G. Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title | Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title_full | Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title_fullStr | Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title_full_unstemmed | Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title_short | Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| title_sort | synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamides related to the anti-tumour drug temozolomide, with appended silicon, benzyl and heteromethyl groups at the 3-position |
| url | https://eprints.nottingham.ac.uk/49226/ https://eprints.nottingham.ac.uk/49226/ https://eprints.nottingham.ac.uk/49226/ |