Synthesis and evaluation of benzoylbenzofurans and isoflavone derivatives as sirtuin 1 inhibitors with antiproliferative effects on cancer cells

dc.contributor.authorSelepe, Mamoalosi A.
dc.contributor.authorKunyane, Phaladi
dc.contributor.authorSeboletswe, Pule
dc.contributor.authorNair, Shankari
dc.contributor.authorCele, Nosipho
dc.contributor.authorEngelbrecht, Monique
dc.contributor.authorJoubert, Daniel Francois
dc.contributor.authorVandevoorde, Charlot
dc.contributor.authorSingh, Parvesh
dc.contributor.authorSonopo, Molahlehi S.
dc.contributor.emailmamoalosi.selepe@up.ac.zaen_US
dc.date.accessioned2023-03-07T09:29:28Z
dc.date.available2023-03-07T09:29:28Z
dc.date.issued2022-11
dc.description.abstractIsoflavone derivatives were prepared from benzoylbenzofuran precursors. The synthesized compounds were analyzed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as high-resolution mass spectrometry (HRMS) to confirm their structures. The benzoylbenzofuran and isoflavone analogues were evaluated for inhibition of sirtuin 1 (SIRT1) and cell proliferation in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Several isoflavone and benzoylbenzofuran derivatives exhibited potent antiproliferative effects against the MDA-MB-231 cancer cell line. Most of the isoflavone derivatives attenuated SIRT1 activity to below 50%. The most active compounds were the isoflavone quinones 38, 39, and 40, at IC50 values of 5.58 ± 0.373, 1.62 ± 0.0720, and 7.24 ± 0.823 μM, respectively. Importantly, the most active compound, 6-methoxy-4′,6′-dimethylisoflavone-2′,5′-quinone (39) displayed SIRT1 inhibitory activity comparable to that of the reference compound, suramin. The in silico docking simulations in the active site of SIRT1 further substantiated the experimental results and explored the binding orientations of potent compounds in the active site of the target.en_US
dc.description.departmentChemistryen_US
dc.description.departmentPhysiologyen_US
dc.description.librarianhj2023en_US
dc.description.sponsorshipThe National Research Foundation of South Africa; the University of Pretoria and the South African Nuclear Energy Corporation (Necsa SOC Ltd).en_US
dc.description.urihttps://www.elsevier.com/locate/bioorgen_US
dc.identifier.citationSelepe, M.A., Kunyane, P., Seboletswe, P. et al. 2022, 'Synthesis and evaluation of benzoylbenzofurans and isoflavone derivatives as sirtuin 1 inhibitors with antiproliferative effects on cancer cells', Bioorganic Chemistry, vol. 128, art. 106101, pp. 1-9, doi : 10.1016/j.bioorg.2022.106101.en_US
dc.identifier.issn0045-2068 (print)
dc.identifier.issn1090-2120 (online)
dc.identifier.other10.1016/j.bioorg.2022.106101
dc.identifier.urihttps://repository.up.ac.za/handle/2263/90003
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rights© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).en_US
dc.subjectHigh-resolution mass spectrometry (HRMS)en_US
dc.subjectBenzoylbenzofuransen_US
dc.subjectIsoflavonesen_US
dc.subjectSirtuin 1 (SIRT1)en_US
dc.subjectMDA-MB-231en_US
dc.subjectNuclear magnetic resonance (NMR)en_US
dc.subjectTriple-negative breast cancer (TNBC)en_US
dc.titleSynthesis and evaluation of benzoylbenzofurans and isoflavone derivatives as sirtuin 1 inhibitors with antiproliferative effects on cancer cellsen_US
dc.typeArticleen_US

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