Isoquinolinequinone N-oxides as anticancer agents effective against drug resistant cell lines

dc.check.date2020-12-18
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorKruschel, Ryan D.
dc.contributor.authorBuzid, Alyah
dc.contributor.authorKhandavilli, Udaya Bhaskara Rao
dc.contributor.authorLawrence, Simon E.
dc.contributor.authorGlennon, Jeremy D.
dc.contributor.authorMcCarthy, Florence O.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderEuropean Cooperation in Science and Technologyen
dc.date.accessioned2020-02-11T15:22:51Z
dc.date.available2020-02-11T15:22:51Z
dc.date.issued2019-12-18
dc.date.updated2020-02-11T15:11:18Z
dc.description.abstractThe isoquinolinequinone (IQQ) pharmacophore is a privileged framework in known cytotoxic natural product families, caulibugulones and mansouramycins. Exploiting both families as a chemical starting point, we report on the structured development of an IQQ N-oxide anticancer framework which exhibits growth inhibition in the nM range across melanoma, ovarian and leukaemia cancer cell lines. A new lead compound (16, R6 = benzyl, R7 = H) exhibits nM GI50 values against 31/57 human tumour cell lines screened as part of the NCI60 panel and shows activity against doxorubicin resistant tumour cell lines. An electrochemical study highlights a correlation between electropositivity of the IQQ N-oxide framework and cytotoxicity. Adduct binding to sulfur based biological nucleophiles glutathione and cysteine was observed in vitro. This new framework possesses significant anticancer potential.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKruschel, R. D., Buzid, A., Khandavilli, U. B. R., Lawrence, S. E., Glennon, J. D. and McCarthy, F. O. (2020) 'Isoquinolinequinone N-oxides as anticancer agents effective against drug resistant cell lines', Organic & Biomolecular Chemistry, 18(3), pp. 557-568. doi: 10.1039/C9OB02441Gen
dc.identifier.doi10.1039/C9OB02441Gen
dc.identifier.endpage568en
dc.identifier.issn1477-0520
dc.identifier.issued3en
dc.identifier.journaltitleOrganic & Biomolecular Chemistryen
dc.identifier.startpage557en
dc.identifier.urihttps://hdl.handle.net/10468/9633
dc.identifier.volume18en
dc.language.isoenen
dc.publisherRoyal Society of Chemistryen
dc.relation.projectEuropean Cooperation in Science and Technology (COST Action CA15135)en
dc.relation.urihttps://pubs.rsc.org/en/content/articlehtml/2020/ob/c9ob02441g
dc.rightshttps://pubs.rsc.org/en/content/articlelanding/2020/OB/C9OB02441Gen
dc.subjectLead compoundsen
dc.subjectAmino acidsen
dc.subjectCell cultureen
dc.subjectCellsen
dc.subjectTumorsen
dc.subjectAnti-cancer agentsen
dc.subjectAnticancer potentialsen
dc.subjectCancer cell linesen
dc.subjectElectrochemical studiesen
dc.subjectGrowth inhibitionen
dc.subjectNatural productsen
dc.subjectPharmacophoresen
dc.subjectResistant cellsen
dc.titleIsoquinolinequinone N-oxides as anticancer agents effective against drug resistant cell linesen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 2 of 2
Loading...
Thumbnail Image
Name:
FMC_OBC_IQQ_Paper_1_CORA_edition.pdf
Size:
436.69 KB
Format:
Adobe Portable Document Format
Description:
Accepted version
Loading...
Thumbnail Image
Name:
Supplementary Information final.pdf
Size:
8.78 MB
Format:
Adobe Portable Document Format
Description:
Supplementary information
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description: