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Título: | Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures | Autor: | Ramos, Catarina I. V. Almeida, Susana P. Lourenço, Leandro M. O. Pereira, Patrícia M. R. Fernandes, Rosa Faustino, M. Amparo F. Tomé, João P. C. Carvalho, Josué Cruz, Carla Neves, M. Graça P. M. S. |
Palavras-chave: | multicharged phthalocyanines; G-Quadruplexes; telomerase inhibition; selectivity; salmon sperm DNA; UV-Vis; hyperchromism; G4-FID; circular dichroism | Data: | 18-Fev-2019 | Editora: | MDPI | Projeto: | This research was funded by QOPNA (FCT UID/QUI/00062/2019), CQE (FCT UID/QUI/0100/2013), and CICS-UBI (FCT UID/Multi/00709/2013) research units, and the FCT projects (PTDC/QUI-QOR/31770/2017, P2020-PTDC/QEQ-SUP/5355/2014), national founds (PIDDAC) and co-financed by the FEDER-Operational Thematic Program for Competitiveness and Internationalization-COMPETE 2020, within the PT2020 Partnership Agreement. C.I.V.R. thanks FCT for her postdoctoral grant (SFRH/BPD/85902/2012). We acknowledge the financial support from FCT/MCTES and Portugal 2020 to the RNEM (LISBOA-01-0145-FEDER-402-022125) and Node IST-Campus Alameda for facilities. Josué Carvalho acknowledges the doctoral fellowship grant SFRH/BD/122953/2016 from FCT and projects ref. IF/00959/2015 financed by Fundo Social Europeu and Programa Operacional Potencial Humano, project Fundação Luso-Americana (FLAD) Healthcare 2020 ref. 45/2018, project MIT-EXPL/BIO/0008/2017 and project UTAP-EXPL/NTec/0015/2017. This work was also supported FCT, Strategic Project UID/NEU/04539/2013 (CNC.IBILI Consortium), COMPETE-FEDER (POCI-01-0145-FEDER-007440) and Centro 2020 Regional Operational Programme: HEALTHYAGING 2020 (CENTRO-01-0145-FEDER-000012); PPBI-POCI-01-0145- FEDER-022122 | Título da revista, periódico, livro ou evento: | Molecules | Volume: | 24 | Número: | 4 | Resumo: | The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells. | URI: | https://hdl.handle.net/10316/107169 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules24040733 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais I&D ICBR - Artigos em Revistas Internacionais |
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Multicharged-phthalocyanines-as-selective-ligands-for-Gquadruplex-DNA-structuresMolecules.pdf | 8.28 MB | Adobe PDF | Ver/Abrir |
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