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dc.contributor.authorHarrison, RJ
dc.contributor.authorReszka, AP
dc.contributor.authorHaider, SM
dc.contributor.authorRomagnoli, B
dc.contributor.authorMorrell, J
dc.contributor.authorRead, MA
dc.contributor.authorGowan, SM
dc.contributor.authorIncles, CM
dc.contributor.authorKelland, LR
dc.contributor.authorNeidle, S
dc.date.accessioned2018-09-10T14:11:17Z
dc.date.issued2004
dc.identifier23
dc.identifier.citationBioorganic & Medicinal Chemistry Letters, 2004, 14 pp. 5845 - 5849
dc.identifier.issn0960-894X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2609
dc.identifier.doi10.1016/j.bmcl.2004.09.037
dc.description.abstractThe synthesis and evaluation of a group of 2,6-, 2,7- and 3,6-bis-aminoalkylamido acridones are reported, which show a similar level of activity against telomerase in vitro compared to their acridine counterparts. Computer modelling and calculations of relative binding energies suggest an equivalent binding mode to human intramolecular G-quadruplex DNA, but with significantly reduced affinity, as a result of the limited delocalisation of the acridone chromophore compared to the acridine system. Thermal melting studies on acridone and acridine quadruplex complexes using a FRET approach support these predictions. Long-term cell proliferation studies at sub-cytotoxic doses with two representative acridones using the SKOV3 cell line, show that neither compound produces growth arrest, in contrast with the effects produced by the tri-substituted acridine compound BRACO-19. It is concluded that telomerase inhibitory activity is a necessary though by itself insufficient property in order for cellular growth arrest to occur at sub-toxic concentrations, and that tight quadruplex binding is also required.
dc.format.extent5845 - 5849
dc.languageeng
dc.language.isoeng
dc.titleEvaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/j.bmcl.2004.09.037
rioxxterms.licenseref.startdate2004
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBioorganic & Medicinal Chemistry Letters
pubs.noteskeywords: Acridone, Telomerase, Quadruplex DNA
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Pharmacology & Stress Response (CPSR)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Pharmacology & Stress Response (CPSR)
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Pharmacology & Stress Response (CPSR)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Pharmacology & Stress Response (CPSR)
pubs.volume14en_US
pubs.embargo.termsNot known
icr.researchteamCancer Pharmacology & Stress Response (CPSR)en_US
dc.contributor.icrauthorGowan, Sharonen


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