Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
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 quadruple...
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doaj-0114b3156a6344569e4b34dfbeb56a1e2020-11-24T20:48:14ZengMDPI AGMolecules1420-30492019-02-0124473310.3390/molecules24040733molecules24040733Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA StructuresCatarina I. V. Ramos0Susana P. Almeida1Leandro M. O. Lourenço2Patrícia M. R. Pereira3Rosa Fernandes4M. Amparo F. Faustino5João P. C. Tomé6Josué Carvalho7Carla Cruz8M. Graça P. M. S. Neves9QOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalQOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalQOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalQOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalCoimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalQOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalCQE & Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, n1, 1049-001 Lisboa, PortugalCICS-UBI—Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, PortugalCICS-UBI—Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, PortugalQOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalThe 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.https://www.mdpi.com/1420-3049/24/4/733multicharged phthalocyaninesG-Quadruplexestelomerase inhibitionselectivitysalmon sperm DNAUV-VishyperchromismG4-FIDcircular dichroism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catarina I. V. Ramos Susana P. Almeida Leandro M. O. Lourenço Patrícia M. R. Pereira Rosa Fernandes M. Amparo F. Faustino João P. C. Tomé Josué Carvalho Carla Cruz M. Graça P. M. S. Neves |
spellingShingle |
Catarina I. V. Ramos Susana P. Almeida Leandro M. O. Lourenço Patrícia M. R. Pereira Rosa Fernandes M. Amparo F. Faustino João P. C. Tomé Josué Carvalho Carla Cruz M. Graça P. M. S. Neves Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures Molecules multicharged phthalocyanines G-Quadruplexes telomerase inhibition selectivity salmon sperm DNA UV-Vis hyperchromism G4-FID circular dichroism |
author_facet |
Catarina I. V. Ramos Susana P. Almeida Leandro M. O. Lourenço Patrícia M. R. Pereira Rosa Fernandes M. Amparo F. Faustino João P. C. Tomé Josué Carvalho Carla Cruz M. Graça P. M. S. Neves |
author_sort |
Catarina I. V. Ramos |
title |
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures |
title_short |
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures |
title_full |
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures |
title_fullStr |
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures |
title_full_unstemmed |
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures |
title_sort |
multicharged phthalocyanines as selective ligands for g-quadruplex dna structures |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-02-01 |
description |
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. |
topic |
multicharged phthalocyanines G-Quadruplexes telomerase inhibition selectivity salmon sperm DNA UV-Vis hyperchromism G4-FID circular dichroism |
url |
https://www.mdpi.com/1420-3049/24/4/733 |
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