Phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonates and phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonamides as new antimicrotubule agents targeting the colchicine-binding site
DC Field | Value | Language |
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dc.contributor.author | Gagné-Boulet, Mathieu | - |
dc.contributor.author | Bouzriba, Chahrazed | - |
dc.contributor.author | Chavez Alvarez, Atziri Corin | - |
dc.contributor.author | Fortin, Sébastien | - |
dc.date.accessioned | 2022-08-04T17:00:28Z | - |
dc.date.available | 2023-03-05T00:00:00Z | - |
dc.date.issued | 2021-03-05 | - |
dc.identifier.issn | 0223-5234 | fr |
dc.identifier.uri | http://hdl.handle.net/20.500.11794/74062 | - |
dc.description.abstract | We recently designed and prepared new families of potent antimicrotubule agents designated as N-phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB–SOs) and phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamides (PIB–SAs). Our previous structure-activity relationship studies (SAR) focused on the aromatic ring B of PIB-SOs and PIB-SAs leaving the impact of the phenylimidazolidin-2-one moiety (ring A) on the binding to the colchicine-binding site (C-BS) poorly studied. Therefore, the aim of the present study was to evaluate the effect of replacing the imidazolidin-2-one (IMZ) group by a pyrrolidin-2-one moiety. To that end, 15 new phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonate (PYB–SO) and 15 phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonamide (PYB-SA) derivatives were designed, prepared, chemically characterised and biologically evaluated. PYB-SOs and PYB-SAs exhibit antiproliferative activity in the low nanomolar to low micromolar range (0.0087–8.6 μM and 0.056–21 μM, respectively) on human HT-1080, HT-29, M21 and MCF7 cancer cell lines. Moreover, they block cell cycle progression in G2/M phase. Immunofluorescence, tubulin affinity and tubulin polymerisation assays show that they cause microtubule depolymerisation by docking the C-BS. In addition, docking assays with the most potent derivatives show binding affinity toward the C-BS and they also exhibit weak or no toxicity toward chick embryos. Finally, physicochemical properties calculated using the SwissADME algorithm show that PYB-SOs and PYB-SAs are promising new families of antimicrotubule agents. | fr |
dc.language | eng | fr |
dc.publisher | Elsevier | fr |
dc.subject | Anticancer agents | fr |
dc.subject | Antimicrotubule agents | fr |
dc.subject | Antimitotics | fr |
dc.subject | Colchicine-binding site inhibitors | fr |
dc.subject | Phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonates | fr |
dc.subject | Phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonamides | fr |
dc.title | Phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonates and phenyl 4-(2-oxopyrrolidin-1-yl)benzenesulfonamides as new antimicrotubule agents targeting the colchicine-binding site | fr |
dc.type | COAR1_1::Texte::Périodique::Revue::Contribution à un journal::Article::Article de recherche | fr |
dcterms.bibliographicCitation | European journal of medicinal chemistry, Vol. 213, 113136 (2021) | fr |
dc.identifier.doi | 10.1016/j.ejmech.2020.113136 | fr |
dc.identifier.pubmed | 33472119 | fr |
dc.subject.rvm | Anticancéreux | fr |
dc.subject.rvm | Benzènesulfonates | fr |
dc.subject.rvm | Microtubules | fr |
dc.subject.rvm | Colchicine -- Inhibiteurs | fr |
rioxxterms.version | Accepted Manuscript | fr |
rioxxterms.version_of_record | https://doi.org/10.1016/j.ejmech.2020.113136 | fr |
rioxxterms.project | NSERC, RGPIN-2016-05069 | fr |
rioxxterms.project.funder_name | Natural Sciences and Engineering Research Council of Canada | fr |
rioxxterms.project.funder_name | Fonds de Recherche du Québec - Santé | fr |
rioxxterms.project.funder_name | CHU de Québec. Centre de recherche | fr |
rioxxterms.project.funder_name | Fonds d'enseignement et de recherche de la Faculté de Pharmacie de l'Université Laval | fr |
ali.license_ref | Attribution - Pas d'Utilisation Commerciale - Pas de Modification CC BY-NC-ND | fr |
ali.license_ref.start_date | 2023-03-05 | fr |
bul.rights.periodeEmbargo | 24 mois | fr |
bul.rights.addendum | Rien | fr |
Collection: | Articles publiés dans des revues avec comité de lecture |
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35. European Journal of Medicinal Chemistry 2021.pdf | 2.58 MB | Adobe PDF | Request a copy |
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