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Phenolic indeno[1,2-b]indoles as ABCG2-selective potent and non-toxic inhibitors stimulating basal ATPase activity.

hal.structure.identifierBases moléculaires et structurales des systèmes infectieux [BMSSI]
hal.structure.identifierDepartment of Biochemistry and Molecular Biology
dc.contributor.authorGOZZI, Gustavo Jabor
hal.structure.identifierBiomolécules Cancer et Chimiorésistances [B2C]
dc.contributor.authorBOUAZIZ, Zouhair
hal.structure.identifierDepartment of Pharmaceutical Sciences [ PGFAR]
dc.contributor.authorWINTER, Evelyn
hal.structure.identifierBases moléculaires et structurales des systèmes infectieux [BMSSI]
dc.contributor.authorDAFLON-YUNES, Nathalia
hal.structure.identifierBases moléculaires et structurales des systèmes infectieux [BMSSI]
dc.contributor.authorHONORAT, Mylène
hal.structure.identifierBiomolécules Cancer et Chimiorésistances [B2C]
dc.contributor.authorGURAGOSSIAN, Nathalie
hal.structure.identifierBiomolécules Cancer et Chimiorésistances [B2C]
dc.contributor.authorMARMINON, Christelle
hal.structure.identifierBases moléculaires et structurales des systèmes infectieux [BMSSI]
hal.structure.identifierDepartment of Biochemistry and Molecular Biology
dc.contributor.authorVALDAMERI, Glaucio
hal.structure.identifierInstitut für Pharmazeutische und Medizinische Chemie
dc.contributor.authorBOLLACKE, Andre
hal.structure.identifierUniversité de Bordeaux, ARNA Laboratory [U869]
dc.contributor.authorGUILLON, Jean
hal.structure.identifierInstitut des Sciences Moléculaires [ISM]
dc.contributor.authorPINAUD, Noël
hal.structure.identifierInstitut de Chimie de la Matière Condensée de Bordeaux [ICMCB]
dc.contributor.authorMARCHIVIE, Mathieu
hal.structure.identifierDepartment of Biochemistry and Molecular Biology
dc.contributor.authorCADENA, Silvia M.
hal.structure.identifierUniversité de Bordeaux, ARNA Laboratory [U869]
dc.contributor.authorJOSE, Joachim
hal.structure.identifierBiomolécules Cancer et Chimiorésistances [B2C]
dc.contributor.authorLE BORGNE, Marc
hal.structure.identifierBases moléculaires et structurales des systèmes infectieux [BMSSI]
dc.contributor.authorDI PIETRO, Attilio
dc.date.issued2015
dc.identifier.issn1177-8881
dc.description.abstractEnKetonic indeno[1,2-b]indole-9,10-dione derivatives, initially designed as human casein kinase II (CK2) inhibitors, were recently shown to be converted into efficient inhibitors of drug efflux by the breast cancer resistance protein ABCG2 upon suited substitutions including a N (5)-phenethyl on C-ring and hydrophobic groups on D-ring. A series of ten phenolic and seven p-quinonic derivatives were synthesized and screened for inhibition of both CK2 and ABCG2 activities. The best phenolic inhibitors were about threefold more potent against ABCG2 than the corresponding ketonic derivatives, and showed low cytotoxicity. They were selective for ABCG2 over both P-glycoprotein and MRP1 (multidrug resistance protein 1), whereas the ketonic derivatives also interacted with MRP1, and they additionally displayed a lower interaction with CK2. Quite interestingly, they strongly stimulated ABCG2 ATPase activity, in contrast to ketonic derivatives, suggesting distinct binding sites. In contrast, the p-quinonic indenoindoles were cytotoxic and poor ABCG2 inhibitors, whereas a partial inhibition recovery could be reached upon hydrophobic substitutions on D-ring, similarly to the ketonic derivatives.
dc.language.isoen
dc.publisherDove Medical Press
dc.title.enPhenolic indeno[1,2-b]indoles as ABCG2-selective potent and non-toxic inhibitors stimulating basal ATPase activity.
dc.typeArticle de revue
dc.identifier.doi10.2147/DDDT.S84982
dc.subject.halChimie
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalDrug Design, Development and Therapy
bordeaux.page3481-3495
bordeaux.volume9
bordeaux.peerReviewedoui
hal.identifierhal-01179426
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01179426v1
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