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dc.contributor.authorChung, Po Yee
dc.contributor.authorLam, Pik Ling
dc.contributor.authorZhou, Yuanyuan
dc.contributor.authorGasparello, Jessica
dc.contributor.authorFinotti, Alessia
dc.contributor.authorChilin, Adriana
dc.contributor.authorMarzaro, Giovanni
dc.contributor.authorGambari, Roberto
dc.contributor.authorBian, Zhaoxiang
dc.contributor.authorKwok, Wai Ming
dc.contributor.authorWong, Wai Yeung
dc.contributor.authorWang, Xi
dc.contributor.authorLam, Alfred King-yin
dc.contributor.authorChan, Albert Sun-chi
dc.contributor.authorLi, Xingshu
dc.contributor.authorMa, Jessica Yuen Wuen
dc.contributor.authorChui, Chung Hin
dc.contributor.authorLam, Kim Hung
dc.contributor.authorTang, Johnny Cheuk On
dc.date.accessioned2019-09-30T03:27:46Z
dc.date.available2019-09-30T03:27:46Z
dc.date.issued2018
dc.identifier.issn2073-4409en_US
dc.identifier.doi10.3390/cells7100177en_US
dc.identifier.urihttp://hdl.handle.net/10072/387910
dc.description.abstractQuinoline core has been shown to possess a promising role in the development of anticancer agents. However, the correlation between its broad spectrum of bioactivity and the underlying mechanism of actions is poorly understood. The present study, with the use of bioinformatics approaches, reported a series of designed molecules which integrated quinoline core and sulfonyl moiety, with the objective of evaluating the substituent and linker effects on anticancer activities and associated mechanistic targets. We identified potent compounds (1h, 2h, 5 and 8) exhibiting significant anticancer effects towards liver cancer cells (Hep3B) with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) relative values of cytotoxicity below 0.40, a value in the range of doxorubicin positive control with the value of 0.12. Bulky substituents and the presence of bromine atom, as well as the presence of sulfonamide linkage, are likely the favorable structural components for molecules exerting a strong anticancer effect. To the best of our knowledge, our findings obtained from chemical synthesis, in vitro cytotoxicity, bioinformatics-based molecular docking analysis (similarity ensemble approach, SEA),and electrophoretic mobility shift assay provided the first evidence in correlation to the anticancer activities of the selected compound 5 with the modulation on the binding of transcription factor NF-κB to its target DNA. Accordingly, compound 5 represented a lead structure for the development of quinoline-based NF-κB inhibitors and this work added novel information on the understanding of the mechanism of action for bioactive sulfonyl-containing quinoline compounds against hepatocellular carcinoma.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherMDPIen_US
dc.relation.ispartofpagefrom177:1en_US
dc.relation.ispartofpageto177:14en_US
dc.relation.ispartofissue10en_US
dc.relation.ispartofjournalCellsen_US
dc.relation.ispartofvolume7en_US
dc.subject.keywordsScience & Technologyen_US
dc.subject.keywordsLife Sciences & Biomedicineen_US
dc.subject.keywordsCell Biologyen_US
dc.subject.keywordsNF-kappa Ben_US
dc.subject.keywordsanticanceren_US
dc.titleTargeting DNA Binding for NF-kappa B as an Anticancer Approach in Hepatocellular Carcinomaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationChung, PY; Lam, PL; Zhou, Y; Gasparello, J; Finotti, A; Chilin, A; Marzaro, G; Gambari, R; Bian, Z; Kwok, WM; Wong, WY; Wang, X; Lam, AK-Y; Chan, AS-C; Li, X; Ma, JYW; Chui, CH; Lam, KH; Tang, JCO, Targeting DNA Binding for NF-kappa B as an Anticancer Approach in Hepatocellular Carcinoma, Cells, 2018, 7 (10), pp. 177:1-177:14en_US
dcterms.dateAccepted2018-10-19
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/en_US
dc.date.updated2019-09-30T03:25:19Z
dc.description.versionPublisheden_US
gro.rights.copyright© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citeden_US
gro.hasfulltextFull Text
gro.griffith.authorLam, Alfred K.


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