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dc.contributor.authorCousin, D.*
dc.contributor.authorHummersone, M.G.*
dc.contributor.authorBradshaw, T.D.*
dc.contributor.authorZhang, J.*
dc.contributor.authorMoody, C.J.*
dc.contributor.authorForeiter, M.B.*
dc.contributor.authorSummers, H.S.*
dc.contributor.authorLewis, W.*
dc.contributor.authorWheelhouse, Richard T.*
dc.contributor.authorStevens, M.F.G.*
dc.date.accessioned2018-01-26T13:36:17Z
dc.date.available2018-01-26T13:36:17Z
dc.date.issued2018
dc.identifier.citationCousin 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.urihttp://hdl.handle.net/10454/14701
dc.descriptionYesen_US
dc.description.abstractA 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.isoenen_US
dc.subjectImidazotetrazineen_US
dc.subjectSynthesis
dc.subjectGlioma
dc.subjectTemozolomide
dc.titleSynthesis 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-positionen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-01-12
dc.date.application2018-01-19
dc.typeArticleen_US
dc.type.versionAccepted manuscripten_US
dc.identifier.doihttps://doi.org/10.1039/C7MD00554G


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