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2018-11-01Zeitschriftenartikel DOI: 10.3390/cells7110192
Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives
dc.contributor.authorMajcher, Urszula
dc.contributor.authorKlejborowska, Greta
dc.contributor.authorMoshari, Mahshad
dc.contributor.authorMaj, Ewa
dc.contributor.authorWietrzyk, Joanna
dc.contributor.authorBartl, Franz
dc.contributor.authorTuszynski, Jack
dc.contributor.authorHuczyński, Adam
dc.date.accessioned2019-08-22T10:49:31Z
dc.date.available2019-08-22T10:49:31Z
dc.date.issued2018-11-01none
dc.date.updated2019-08-01T05:01:03Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/21188
dc.description.abstractMicrotubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.eng
dc.description.sponsorshipNarodowe Centrum Nauki
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectcolchicine binding site inhibitoreng
dc.subjectβ-tubulin affinityeng
dc.subjectantimitotic agenteng
dc.subjectantiproliferative activityeng
dc.subjectthiocolchicineeng
dc.subject.ddc570 Biologienone
dc.titleAntiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivativesnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/21188-4
dc.identifier.doi10.3390/cells7110192none
dc.identifier.doihttp://dx.doi.org/10.18452/20419
dc.type.versionpublishedVersionnone
local.edoc.pages16none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn2073-4409
dcterms.bibliographicCitation.journaltitleCellsnone
dcterms.bibliographicCitation.volume7none
dcterms.bibliographicCitation.issue11none
dcterms.bibliographicCitation.articlenumber192none
dcterms.bibliographicCitation.originalpublishernameMDPInone
dcterms.bibliographicCitation.originalpublisherplaceBaselnone
bua.import.affiliationMajcher, Urszula; Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland,none
bua.import.affiliationKlejborowska, Greta; Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland,none
bua.import.affiliationMoshari, Mahshad; Department of Chemistry, University of Alberta, Edmonton, AB T6G 1Z2, Canada,none
bua.import.affiliationMaj, Ewa; Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland,none
bua.import.affiliationWietrzyk, Joanna; Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland,none
bua.import.affiliationBartl, Franz; Institut für Biologie, AG Biophysikalische Chemie, Humboldt Universität zu Berlin, Invalidenstr, 42, 10099 Berlin, Germany,none
bua.import.affiliationTuszynski, Jack A.; Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada,none
bua.import.affiliationHuczyński, Adam; Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland,none
bua.departmentLebenswissenschaftliche Fakultätnone

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