A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold.

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dc.contributor.author Li-Zhulanov, Nikolai S en
dc.contributor.author Zakharenko, Alexandra L en
dc.contributor.author Chepanova, Arina A en
dc.contributor.author Patel, Jinal en
dc.contributor.author Zafar, Ayesha en
dc.contributor.author Volcho, Konstantin P en
dc.contributor.author Salakhutdinov, Nariman F en
dc.contributor.author Reynisson, Johannes en
dc.contributor.author Leung, Ka Ho Ivanhoe en
dc.contributor.author Lavrik, Olga I en
dc.date.accessioned 2019-03-11T20:27:20Z en
dc.date.issued 2018-09-26 en
dc.identifier.citation Molecules 23(10) 26 Sep 2018 en
dc.identifier.issn 1420-3049 en
dc.identifier.uri http://hdl.handle.net/2292/45895 en
dc.description.abstract Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Molecules (Basel, Switzerland) 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.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Humans en
dc.subject Benzopyrans en
dc.subject Phosphoric Diester Hydrolases en
dc.subject Phosphodiesterase Inhibitors en
dc.subject Structure-Activity Relationship en
dc.subject Models, Molecular en
dc.title A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold. en
dc.type Journal Article en
dc.identifier.doi 10.3390/molecules23102468 en
pubs.issue 10 en
pubs.volume 23 en
dc.rights.holder Copyright: The authors en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 753788 en
pubs.org-id Academic Services en
pubs.org-id Examinations en
pubs.org-id Science en
pubs.org-id Chemistry en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1420-3049 en
pubs.record-created-at-source-date 2018-09-29 en
pubs.dimensions-id 30261631 en

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