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dc.contributor.authorHamdy, Rania
dc.contributor.authorElseginy, Samia
dc.contributor.authorZiedan, Noha
dc.contributor.authorEl-Sadek, Mohamed
dc.contributor.authorLashin, El-Said
dc.contributor.authorJones, Arwyn T
dc.contributor.authorWestwell, Andrew D
dc.date.accessioned2021-01-13T11:40:39Z
dc.date.available2021-01-13T11:40:39Z
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624165/paper.pdf?sequence=1
dc.identifier.citationHamdy, R., Elseginy, S. A., Ziedan, N. I., El-Sadek, M., Lashin, E., Jones, A. T., & Westwell, A. D. (2020). Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2. International Journal of Molecular Sciences, 21(23), 8980.en_US
dc.identifier.urihttp://hdl.handle.net/10034/624165
dc.description.abstractA series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a–m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a–m in the presence of phosphorus oxychloride. New compounds 4a–m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52–0.88 μM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.en_US
dc.publisherMDPIen_US
dc.relation.urlhttps://www.mdpi.com/1422-0067/21/23/8980en_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDrug designen_US
dc.subjectOrganic synthesisen_US
dc.subjectAnti-cancer drug discoveryen_US
dc.titleDesign, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2en_US
dc.typeArticleen_US
dc.identifier.eissn1422-0067en_US
dc.contributor.departmentUniversity of Chester; Cardiff University; Zagazig University; Bristol University; University of Sharjahen_US
dc.identifier.journalInternational Journal of Molecular sciencesen_US
or.grant.openaccessYesen_US
rioxxterms.funderN/Aen_US
rioxxterms.identifier.projectunfundeden_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecordhttps://doi.org/10.3390/ijms21238980en_US
rioxxterms.licenseref.startdate2020-11-26
dcterms.dateAccepted2020-11-21
rioxxterms.publicationdate2020-11-26
dc.date.deposited2021-01-13en_US
dc.indentifier.issn1661-6596en_US


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CC0 1.0 Universal
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