Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors

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dc.citation.epage5808en_US
dc.citation.issueNumber12en_US
dc.citation.spage5798en_US
dc.citation.volumeNumber22en_US
dc.contributor.authorKaplan-Ozen, C.en_US
dc.contributor.authorTekiner-Gulbas, B.en_US
dc.contributor.authorFoto, E.en_US
dc.contributor.authorYildiz I.en_US
dc.contributor.authorDiril, N.en_US
dc.contributor.authorAki, E.en_US
dc.contributor.authorYalcin I.en_US
dc.date.accessioned2016-02-08T09:33:39Z
dc.date.available2016-02-08T09:33:39Z
dc.date.issued2013en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractBenzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIα inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIα inhibitor with the lowest IC50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groove-binding agent. BM3 initially bound to the DNA topoisomerase IIα enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIα inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIα inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent. © 2013 Springer Science+Business Media New York.en_US
dc.identifier.doi10.1007/s00044-013-0577-5en_US
dc.identifier.issn10542523
dc.identifier.urihttp://hdl.handle.net/11693/20709
dc.language.isoEnglishen_US
dc.relation.isversionofhttp://dx.doi.org/10.1007/s00044-013-0577-5en_US
dc.source.titleMedicinal Chemistry Researchen_US
dc.subjectAnticancer drugsen_US
dc.subjectBenzothiazole derivativesen_US
dc.subjectCatalytic inhibitoren_US
dc.subjectDNA bindingen_US
dc.subjectHuman topoisomerase IIαen_US
dc.subjectIntercalationen_US
dc.subject4 methylbenzensulfonateen_US
dc.subjectantineoplastic agenten_US
dc.subjectbenzothiazole derivativeen_US
dc.subjectdeoxyribonuclease Ien_US
dc.subjectDNA Aen_US
dc.subjectDNA topoisomeraseen_US
dc.subjectDNA topoisomerase (ATP hydrolysing)en_US
dc.subjectintercalating agenten_US
dc.subjectunclassified drugen_US
dc.subjectarticleen_US
dc.subjectDNA bindingen_US
dc.subjectdrug efficacyen_US
dc.subjecthumanen_US
dc.subjectIC 50en_US
dc.subjectprotein DNA interactionen_US
dc.titleBenzothiazole derivatives as human DNA topoisomerase IIα inhibitorsen_US
dc.typeArticleen_US

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