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dc.contributor.authorAbd Al Moaty, Mohamed N.
dc.contributor.authorEl Kilany, Yeldez
dc.contributor.authorAwad, Laila F.
dc.contributor.authorSoliman, Saied M.
dc.contributor.authorBarakat, Assem
dc.contributor.authorIbrahim, Nihal A.
dc.contributor.authorAbu-Serie, Marwa M.
dc.contributor.authorHaukka, Matti
dc.contributor.authorEl-Yazbi, Amira
dc.contributor.authorTeleb, Mohamed
dc.date.accessioned2024-05-23T06:12:49Z
dc.date.available2024-05-23T06:12:49Z
dc.date.issued2024
dc.identifier.citationAbd Al Moaty, M. N., El Kilany, Y., Awad, L. F., Soliman, S. M., Barakat, A., Ibrahim, N. A., Abu-Serie, M. M., Haukka, M., El-Yazbi, A., & Teleb, M. (2024). Triggering Breast Cancer Apoptosis via Cyclin-Dependent Kinase Inhibition and DNA Damage by Novel Pyrimidinone and 1,2,4-Triazolo[4,3-a]pyrimidinone Derivatives. <i>ACS Omega</i>, <i>Early online</i>. <a href="https://doi.org/10.1021/acsomega.4c00466" target="_blank">https://doi.org/10.1021/acsomega.4c00466</a>
dc.identifier.otherCONVID_213523576
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/95096
dc.description.abstractCombinations of apoptotic inducers are common clinical practice in breast cancer. However, their efficacy is limited by the heterogeneous pharmacokinetic profiles. An advantageous alternative is merging their molecular entities in hybrid multitargeted scaffolds exhibiting synergistic activities and uniform distribution. Herein, we report apoptotic inducers simultaneously targeting DNA and CDK-2 (cyclin-dependent kinase-2) inspired by studies revealing that CDK-2 inhibition sensitizes breast cancer to DNA-damaging agents. Accordingly, rationally substituted pyrimidines and triazolopyrimidines were synthesized and assayed by MTT against MCF-7, MDA-MB231, and Wi-38 cells compared to doxorubicin. The N-(4-amino-2-((2-hydrazinyl-2-oxoethyl)thio)-6-oxo-1,6-dihydropyrimidin-5-yl)acetamide 5 and its p-nitrophenylhydrazone 8 were the study hits against MCF-7 (IC50 = 0.050 and 0.146 μM) and MDA-MB231 (IC50 = 0.826 and 0.583 μM), induced DNA damage at 10.64 and 30.03 nM, and inhibited CDK-2 (IC50 = 0.172 and 0.189 μM). 5 induced MCF-7 apoptosis by 46.75% and disrupted cell cycle during S phase. Docking and MD simulations postulated their stable key interactions.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofseriesACS Omega
dc.rightsCC BY-NC-ND 4.0
dc.subject.otherapoptosis
dc.subject.othercancer
dc.subject.otherfluorescence
dc.subject.othergenetics
dc.subject.othermixtures
dc.titleTriggering Breast Cancer Apoptosis via Cyclin-Dependent Kinase Inhibition and DNA Damage by Novel Pyrimidinone and 1,2,4-Triazolo[4,3-a]pyrimidinone Derivatives
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202405233860
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Chemistryen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.relation.issn2470-1343
dc.relation.volumeEarly online
dc.type.versionpublishedVersion
dc.rights.copyright© 2024 the Authors
dc.rights.accesslevelopenAccessfi
dc.subject.ysoseokset
dc.subject.ysofluoresenssi
dc.subject.ysoperinnöllisyystiede
dc.subject.ysosyöpätaudit
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p13887
jyx.subject.urihttp://www.yso.fi/onto/yso/p3265
jyx.subject.urihttp://www.yso.fi/onto/yso/p5147
jyx.subject.urihttp://www.yso.fi/onto/yso/p678
dc.rights.urlhttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.relation.doi10.1021/acsomega.4c00466
jyx.fundinginformationThe author would like to extend their sincere appreciation to the Researchers Supporting Project (RSP2024R64), King Saud University, Riyadh, Saudi Arabia.
dc.type.okmA1


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