Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates.

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dc.contributor.author Giddens, Anna en
dc.contributor.author Lee, Ho en
dc.contributor.author Lu, Guo-Liang en
dc.contributor.author Miller, Christian en
dc.contributor.author Guo, Jun en
dc.contributor.author Lewis Phillips, Gail D en
dc.contributor.author Pillow, Thomas H en
dc.contributor.author Tercel, Moana en
dc.date.accessioned 2019-11-04T19:38:58Z en
dc.date.issued 2016-11 en
dc.identifier.issn 0968-0896 en
dc.identifier.uri http://hdl.handle.net/2292/48826 en
dc.description.abstract A Pd-catalysed amination method is used to convert seco-CBI, a synthetic analogue of the alkylating subunit of the duocarmycin natural products, from the phenol to amino form. This allows efficient enantioselective access to the more potent S enantiomer of aminoCBI and its incorporation into analogues of DNA minor groove cross-linking agents. Evaluation in a panel of nine human tumour cell lines shows that the bifunctional agents containing aminoCBI are generally less cytotoxic than their phenolCBI analogues and more susceptible to P-glycoprotein-mediated resistance. However, all bifunctional agents are potent cytotoxins, some in the sub-pM IC50 range, with in vitro properties that compare favourably with established microtubule-targeted ADC payloads. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Bioorganic & medicinal chemistry en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Cell Line, Tumor en
dc.subject Humans en
dc.subject Pyrrolidinones en
dc.subject Indoles en
dc.subject Antineoplastic Agents en
dc.subject Antibodies en
dc.subject Cross-Linking Reagents en
dc.subject Drug Screening Assays, Antitumor en
dc.subject Cell Proliferation en
dc.subject Molecular Structure en
dc.subject Structure-Activity Relationship en
dc.subject Dose-Response Relationship, Drug en
dc.subject Cell Cycle Checkpoints en
dc.title Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bmc.2016.09.068 en
pubs.issue 22 en
pubs.begin-page 6075 en
pubs.volume 24 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 27745990 en
pubs.end-page 6081 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Journal Article en
pubs.elements-id 544182 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1464-3391 en
pubs.record-created-at-source-date 2016-10-18 en
pubs.dimensions-id 27745990 en


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