Targeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives

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dc.authoridMiranda, André/0000-0001-9787-3446
dc.authoridGano, Lurdes/0000-0001-7186-2060
dc.authoridBelchior, Ana/0000-0002-6010-0316
dc.authoridBotelho, Maria Filomena/0000-0001-7202-1650
dc.authoridPaulo, Antonio/0000-0002-9164-0913
dc.authoridFernandes, Celia/0000-0002-2119-8293
dc.authoridMoreira, David/0000-0002-4579-3310
dc.contributor.authorPalma, Elisa
dc.contributor.authorIchedef, Cigdem
dc.contributor.authorFernandes, Celia
dc.contributor.authorBelchior, Ana
dc.contributor.authorRaposinho, Paula
dc.contributor.authorGano, Lurdes
dc.contributor.authorMiranda, Andre
dc.date.accessioned2024-08-31T07:50:15Z
dc.date.available2024-08-31T07:50:15Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractThe main goal of this work was to elucidate the potential relevance of (radio)metal chelates of Tc-99m and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. Tc-99m provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural Tc-99m(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz-Tc-99m (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey [TUBITAK-2219]; FCT; Santander Totta - Bolsas de Incentivo a Doutoramento (BID) - UBI-Santander Totta 2022; Faculdade de Ciencias [PTDC/MED-QUI/1554/2020]; FCT; FCT/MCT [UIDB/00709/2020, POCI-01-0145-FEDER-022122, ROTEIRO/0031/2013-PINFRA/22161/2016, CENTRO-01-0145-FEDER-181235]; PPBI-Portuguese Platform of BioImaging and Portuguese NMR Network [UIDB/04539/2020]; FEDER through COMPETE 2020; POCI; PORL; PIDDAC; PAPILOMA [UIDP/04539/2020]; Center for Innovative Biomedicine and Biotechnology (CIBB) [2021.04785.BD, 2023.02001.BD]; Associated Laboratory funding [NRC-LPCC]; [UIDP/00709/2020]; [UID/Multi/04349/2019]; [LA/P/0058/2020]; Vinnova [2021-04785] Funding Source: Vinnovaen_US
dc.description.sponsorshipCigdem & Idot;chedef acknowledge funding support for post-doctoral fellowship provided by The Scientific and Technological Research Council of Turkey (TUBITAK-2219). Andre Miranda and David Moreira acknowledge doctoral fellowship grants from FCT references 2021.04785.BD and 2023.02001.BD, respectively, and the research fellow granted by Santander Totta - Bolsas de Incentivo a Doutoramento (BID) - UBI-Santander Totta 2022, Faculdade de Ciencias. Pedro Lourenco acknowledges the research fellowship grant financed by FCT to CICS-UBI reference UIDP/00709/2020. Thanks are due to FCT/MCT for the financial support through the projects UID/Multi/04349/2019 and PTDC/MED-QUI/1554/2020, UIDB/00709/2020, POCI-01-0145-FEDER-022122 and through the PPBI-Portuguese Platform of BioImaging and Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016), with national funds and, where applicable, co-financed by the FEDER through COMPETE 2020, POCI, PORL and PIDDAC. C.C. acknowledges the grant from project PAPILOMA ref. CENTRO-01-0145-FEDER-181235, NRC-LPCC Bolsa Dr Rocha Alves 2022, and Instruct-ERIC Pilot R&D application ID 2473. The authors would like to thank Raquel Alves from the Laboratory of Oncobiology and Hematology (LOH), from the Faculty of Medicine of the University of Coimbra for the technical support for flow cytometry analysis. FCT supports the Center for Innovative Biomedicine and Biotechnology (CIBB) through the Strategic Projects UIDB/04539/2020, UIDP/04539/2020 and the Associated Laboratory funding LA/P/0058/2020.en_US
dc.identifier.doi10.1002/chem.202400285
dc.identifier.issn0947-6539
dc.identifier.issn1521-3765
dc.identifier.issue22en_US
dc.identifier.pmid38386665en_US
dc.identifier.scopus2-s2.0-85186913673en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1002/chem.202400285
dc.identifier.urihttps://hdl.handle.net/11454/105170
dc.identifier.volume30en_US
dc.identifier.wosWOS:001181275200001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-V C H Verlag Gmbhen_US
dc.relation.ispartofChemistry-A European Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240831_Uen_US
dc.subjectRheniumen_US
dc.subjectTechnetium-99 Men_US
dc.subjectPyridostatinen_US
dc.subjectG-Quadruplex Dannen_US
dc.subjectAnticancer Agentsen_US
dc.titleTargeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivativesen_US
dc.typeArticleen_US

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