dc.contributor.author | Mujumdar, Prashant | |
dc.contributor.author | Kopecka, Joanna | |
dc.contributor.author | Bua, Silvia | |
dc.contributor.author | Supuran, Claudiu T | |
dc.contributor.author | Riganti, Chiara | |
dc.contributor.author | Poulsen, Sally-Ann | |
dc.date.accessioned | 2019-06-10T01:35:16Z | |
dc.date.available | 2019-06-10T01:35:16Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.doi | 10.1021/acs.jmedchem.9b00282 | |
dc.identifier.uri | http://hdl.handle.net/10072/385109 | |
dc.description.abstract | The 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.relation.ispartofpagefrom | 4174 | |
dc.relation.ispartofpageto | 4192 | |
dc.relation.ispartofissue | 8 | |
dc.relation.ispartofjournal | JOURNAL OF MEDICINAL CHEMISTRY | |
dc.relation.ispartofvolume | 62 | |
dc.subject.fieldofresearch | Medicinal and biomolecular chemistry | |
dc.subject.fieldofresearch | Organic chemistry | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3404 | |
dc.subject.fieldofresearchcode | 3405 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.title | Carbonic Anhydrase XII Inhibitors Overcome Temozolomide Resistance in Glioblastoma | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dc.description.version | Accepted Manuscript (AM) | |
gro.rights.copyright | This 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.hasfulltext | Full Text | |
gro.griffith.author | Poulsen, Sally-Ann | |