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
dc.contributor.author | Cousin, D. | * |
dc.contributor.author | Hummersone, M.G. | * |
dc.contributor.author | Bradshaw, T.D. | * |
dc.contributor.author | Zhang, J. | * |
dc.contributor.author | Moody, C.J. | * |
dc.contributor.author | Foreiter, M.B. | * |
dc.contributor.author | Summers, H.S. | * |
dc.contributor.author | Lewis, W. | * |
dc.contributor.author | Wheelhouse, Richard T. | * |
dc.contributor.author | Stevens, M.F.G. | * |
dc.date.accessioned | 2018-01-26T13:36:17Z | |
dc.date.available | 2018-01-26T13:36:17Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Cousin D, Hummersone MG, Bradshaw TD et al (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. 9(3): 545-553. | en_US |
dc.identifier.uri | http://hdl.handle.net/10454/14701 | |
dc.description | Yes | en_US |
dc.description.abstract | 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. | en_US |
dc.language.iso | en | en_US |
dc.subject | Imidazotetrazine | en_US |
dc.subject | Synthesis | |
dc.subject | Glioma | |
dc.subject | Temozolomide | |
dc.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 | en_US |
dc.status.refereed | Yes | en_US |
dc.date.Accepted | 2018-01-12 | |
dc.date.application | 2018-01-19 | |
dc.type | Article | en_US |
dc.type.version | Accepted manuscript | en_US |
dc.identifier.doi | https://doi.org/10.1039/C7MD00554G |