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dc.contributor.authorMann, J
dc.contributor.authorBaron, A
dc.contributor.authorOpoku-Boahen, Y
dc.contributor.authorJohansson, E
dc.contributor.authorParkinson, G
dc.contributor.authorKelland, LR
dc.contributor.authorNeidle, S
dc.date.accessioned2018-09-18T10:36:49Z
dc.date.issued2001-01-18
dc.identifier2
dc.identifier.citationJOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 pp. 138 - 144
dc.identifier.issn0022-2623
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2772
dc.identifier.doi10.1021/jm000297b
dc.description.abstractThe synthesis and evaluation of the novel head-to-head bisbenzimidazole compound 2,2-bis[4’-(3 “ -dimethylamino- 1 “ -propyloxy)phenyl]-5,5-bi-1H-benzimidazole is described. An X-ray crystallographic study of a complex with the DNA dodecanucleotide sequence d(CGCGAATTCGCG) shows the compound bound in the A/T minor groove region of a B-DNA duplex and that the head-to-head bisbenzimidazole motif hydrogen-bonds to the edges of all four consecutive A:T base pairs. The compound showed potent growth inhibition with a mean IC50 across an ovarian carcinoma cell line panel of 0.31 muM, with no significant cross-resistance in two acquired cisplatin-resistant cell lines and a low level of cross-resistance in the P-glycoprotein overexpressing acquired doxorubicin-resistant cell line. Studies with the hollow fiber assay and in vivo tumor xenografts showed some evidence of antitumor activity.
dc.format.extent138 - 144
dc.languageeng
dc.language.isoeng
dc.titleA new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity
dc.typeJournal Article
rioxxterms.versionofrecord10.1021/jm000297b
rioxxterms.licenseref.startdate2001-01-18
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJOURNAL OF MEDICINAL CHEMISTRY
pubs.notesunique-id: ISI:000166504900002
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume44
pubs.embargo.termsNot known
dc.contributor.icrauthorKelland, Lloyden
dc.contributor.icrauthorNeidle, Stephenen


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