<i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands
Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expres...
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MDPI AG
2023-08-01
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| author | Nuno M. M. Moura José A. S. Cavaleiro Maria Graça P. M. S. Neves Catarina I. V. Ramos |
| author_facet | Nuno M. M. Moura José A. S. Cavaleiro Maria Graça P. M. S. Neves Catarina I. V. Ramos |
| author_sort | Nuno M. M. Moura |
| collection | DOAJ |
| description | Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expression, by an effective stabilisation of G-quadruplexes (G4) DNA structures, is being considered as a promising strategy in cancer therapies. When evaluating the potential of a ligand for telomerase inhibition, the selectivity towards quadruplex versus duplex DNA is a fundamental attribute due to the large amount of double-stranded DNA in the cellular nucleus. This study reports the evaluated efficacy of three tetracationic <i>opp</i>-dibenzoporphyrins, a free base, and the corresponding zinc(II) and nickel(II) complexes, to stabilise G4 structures, namely the telomeric DNA sequence (AG<sub>3</sub>(T<sub>2</sub>AG<sub>3</sub>)<sub>3</sub>). In order to evaluate the selectivity of these ligands towards G4 structures, their interaction towards DNA calf thymus, as a double-strand DNA sequence, were also studied. The data obtained by using different spectroscopic techniques, such as ultraviolet-visible, fluorescence, and circular dichroism, suggested good affinity of the free-base porphyrin and of its zinc(II) complex for the considered DNA structures, both showing a pattern of selectivity for the telomeric G4 structure. A pattern of aggregation in aqueous solution was detected for both Zn(II) and Ni(II) metallo dibenzoporphyrins and the ability of DNA sequences to induce ligand disaggregation was observed. |
| first_indexed | 2024-03-10T23:17:23Z |
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| language | English |
| last_indexed | 2024-03-10T23:17:23Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-683c0364f53c4e4d9d20de602ea525442023-11-19T08:34:18ZengMDPI AGMolecules1420-30492023-08-012817631810.3390/molecules28176318<i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA LigandsNuno M. M. Moura0José A. S. Cavaleiro1Maria Graça P. M. S. Neves2Catarina I. V. Ramos3LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalSince the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expression, by an effective stabilisation of G-quadruplexes (G4) DNA structures, is being considered as a promising strategy in cancer therapies. When evaluating the potential of a ligand for telomerase inhibition, the selectivity towards quadruplex versus duplex DNA is a fundamental attribute due to the large amount of double-stranded DNA in the cellular nucleus. This study reports the evaluated efficacy of three tetracationic <i>opp</i>-dibenzoporphyrins, a free base, and the corresponding zinc(II) and nickel(II) complexes, to stabilise G4 structures, namely the telomeric DNA sequence (AG<sub>3</sub>(T<sub>2</sub>AG<sub>3</sub>)<sub>3</sub>). In order to evaluate the selectivity of these ligands towards G4 structures, their interaction towards DNA calf thymus, as a double-strand DNA sequence, were also studied. The data obtained by using different spectroscopic techniques, such as ultraviolet-visible, fluorescence, and circular dichroism, suggested good affinity of the free-base porphyrin and of its zinc(II) complex for the considered DNA structures, both showing a pattern of selectivity for the telomeric G4 structure. A pattern of aggregation in aqueous solution was detected for both Zn(II) and Ni(II) metallo dibenzoporphyrins and the ability of DNA sequences to induce ligand disaggregation was observed.https://www.mdpi.com/1420-3049/28/17/6318dibenzoporphyrinsG-quadruplexestelomerase inhibitionselectivityUV-Visfluorescence |
| spellingShingle | Nuno M. M. Moura José A. S. Cavaleiro Maria Graça P. M. S. Neves Catarina I. V. Ramos <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands Molecules dibenzoporphyrins G-quadruplexes telomerase inhibition selectivity UV-Vis fluorescence |
| title | <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands |
| title_full | <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands |
| title_fullStr | <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands |
| title_full_unstemmed | <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands |
| title_short | <i>opp</i>-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands |
| title_sort | i opp i dibenzoporphyrin pyridinium derivatives as potential g quadruplex dna ligands |
| topic | dibenzoporphyrins G-quadruplexes telomerase inhibition selectivity UV-Vis fluorescence |
| url | https://www.mdpi.com/1420-3049/28/17/6318 |
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