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dc.contributor.authorMujumdar, Prashant
dc.contributor.authorKopecka, Joanna
dc.contributor.authorBua, Silvia
dc.contributor.authorSupuran, Claudiu T
dc.contributor.authorRiganti, Chiara
dc.contributor.authorPoulsen, Sally-Ann
dc.date.accessioned2019-06-10T01:35:16Z
dc.date.available2019-06-10T01:35:16Z
dc.date.issued2019
dc.identifier.issn0022-2623
dc.identifier.doi10.1021/acs.jmedchem.9b00282
dc.identifier.urihttp://hdl.handle.net/10072/385109
dc.description.abstractThe natural product primary sulfonamide, psammaplin C (1), when used in combination with clinically used chemotherapeutic drugs, including temozolomide, reverses multidrug resistance and increases survival in glioblastoma, a highly aggressive primary brain tumor. We showed previously that the mechanism of action of 1 is novel, acting to indirectly interfere with P-glycoprotein drug efflux activity as a consequence of carbonic anhydrase XII (CA XII) inhibition. To build structure–activity relationships, 45 derivatives of 1 were designed, synthesized, and evaluated against a panel of CA isoforms. Compound 55 was identified as a potent inhibitor of CA XII (Ki = 0.56 nM) and was investigated in vitro and in vivo using samples from glioblastoma patients. The results strengthen the possibility that co-therapy of temozolomide with a CA XII inhibitor may more effectively treat glioblastoma by suppressing an important temozolomide resistance mechanism.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAMER CHEMICAL SOC
dc.relation.ispartofpagefrom4174
dc.relation.ispartofpageto4192
dc.relation.ispartofissue8
dc.relation.ispartofjournalJOURNAL OF MEDICINAL CHEMISTRY
dc.relation.ispartofvolume62
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode3214
dc.titleCarbonic Anhydrase XII Inhibitors Overcome Temozolomide Resistance in Glioblastoma
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyrightThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jmedchem.9b00282
gro.hasfulltextFull Text
gro.griffith.authorPoulsen, Sally-Ann


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