Interaction of metal complexes with nucleic acids

Suntharalingam, Kogularamanan; Vilar, Ramón

doi:10.1039/c1ic90027g

Cited by 8 publications

(2 citation statements)

References 96 publications

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“…Nowadays, an active research area is focused on the development of new metallodrugs capable of interacting with DNA, and organometallic ruthenium complexes are promising candidates to this aim. − Over the past few years, a huge amount of work has been published on the synthesis, cytotoxicity, and DNA binding ability of this type of compounds; in particular, clinical trials have been done on NAMI-A and KP1019, whose action is based on the activation by reduction of Ru(III) to Ru(II). Moreover, synthesized Ru(II) arene complexes such as RM175 or RAPTA-T have shown both in vitro and in vivo anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activity and DNA Binding of a Bifunctional Ru(II) Arene Aqua-Complex with the 2,4-Diamino-6-(2-pyridyl)-1,3,5-triazine Ligand

et al. 2013

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The synthesis and full characterization of the new aqua-complex [(η(6)-p-cymene)Ru(OH2)(κ(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase derivative [(η(6)-p-cymene)Ru(9-MeG)(κ(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2, where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9-methylguanine, are reported here. The crystal structures of both [4](PF6)2 and the chloro complex [(η(6)-p-cymene)RuCl(κ(2)-N,N-2-pydaT)](PF6), [1](PF6), have been elucidated by X-ray diffraction. The former provided relevant information regarding the interaction of the metallic fragment [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7 site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional interaction (covalent and partially intercalated) between the [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by kinetic, circular dichroism, viscometry, and thermal denaturation experiments. The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G) covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a bifunctional complex. The dissociation rate of the intercalated fragment is slow, and this confers additional interest to [2](BF4)2 in view of the likely correlation between slow dissociation and biological activity, on the assumption that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH-dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0 μM at pH = 7.4; IC50 = 6.58 μM at pH = 6.5). What is more, complex [2](BF4)2 is not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis), of 0.28, and it shows moderate selectivity toward the cancer cell lines, in particular, A2780cis (IC50 = 3.0 5 ± 0.08 μM), relative to human lung fibroblast cells (MRC-5; IC50 = 24 μM), the model for healthy cells.

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Section: Introductionmentioning

confidence: 99%

Anticancer Activity and DNA Binding of a Bifunctional Ru(II) Arene Aqua-Complex with the 2,4-Diamino-6-(2-pyridyl)-1,3,5-triazine Ligand

et al. 2013

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“…Investigations on DNA cleavage and developments of efficient chemical nucleases have attracted wide interest owing to their potential applications as promising therapeutic agents as well as diagnostic structural probes to analyze DNA information. Among all the chemical nucleases reported so far, transition metal complexes have obvious advantages because metal complexes with natural cationic character particularly favor the redox, hydrolysis and other photoreactions, thus leading to strong affinity to DNA 59,60 . For example, [Cu(phen) 2 ] + units have been widely studied as chemical nucleases for highly efficient DNA cleavage since the redox properties of the metal could not only promote the reactive oxygen species (ROS) generation but also have strong noncovalent interactions with DNA 61 .…”

Section: Resultsmentioning

confidence: 99%

Efficient self-assembly of heterometallic triangular necklace with strong antibacterial activity

Shi

Phan³

et al. 2020

Nat Commun

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Sophisticated mechanically interlocked molecules (MIMs) with interesting structures, properties and applications have attracted great interest in the field of supramolecular chemistry. We herein report a highly efficient self-assembly of heterometallic triangular necklace 1 containing Cu and Pt metals with strong antibacterial activity. Single-crystal X-ray analysis shows that the finely arranged triangular necklace 1 has two racemic enantiomers in its solid state with intriguing packing motif. The superior antibacterial activity of necklace 1 against both standard and clinically drug-resistant pathogens implies that the presence of Cu(I) center and platinum(II) significantly enhance the bacterium-binding/damaging activity, which is mainly attributed to the highly positively charged nature, the possible synergistic effect of heterometals in the necklace, and the improved stability in culture media. This work clearly discloses the structure-property relationships that the existence of two different metal centers not only facilitates successful construction of heterometallic triangular necklace but also endows it with superior nuclease properties and antibacterial activities.

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In vitro investigation of biophysical interactions between Ag(I) complexes of bis(methyl)(thia/selena)salen and ct‐DNA via multi‐spectroscopic, physicochemical and molecular docking methods along with cytotoxicity study

et al. 2021

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Four silver(I) (Ag(I)) complexes: 1.PF6, 2.PF6, 1.ClO4 and 2.ClO4 of bis(methyl)thia salen (1) and bis (methyl)selena salen (2) with two different counter anions (PF6− and ClO4−) have been investigated for DNA binding properties. In vitro interactional association between the Ag(I) complexes and ct‐DNA has been examined by performing spectroscopic titrations on absorption spectrophotometer and fluorescence spectrophotometer. A competitive binding study has also been done using a fluorescence spectrophotometer with ethidium bromide as a classical intercalator. The spectroscopic methods revealed a major groove. Viscometry and agarose gel electrophoresis experiments have also been performed as physicochemical methods to confirm the binding of complex molecules with DNA. Molecular docking analysis has been executed to obtain the theoretical insight into the mode of binding. The docking study demonstrated the major groove binding of all four complexes to the DNA with electrostatic metal–phosphate interactions (between the metal and the backbone of DNA) and hydrophobic interactions. Cytotoxicity of the complexes has been studied on the Human Fibroblast foreskin (HFF) cell line. The cytotoxicity results showed positive gesture for moving ahead to the next level of screening; the values were above 10 μM which are appreciated for the normal cell lines.

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Interaction of metal complexes with nucleic acids

Cited by 8 publications

References 96 publications

Anticancer Activity and DNA Binding of a Bifunctional Ru(II) Arene Aqua-Complex with the 2,4-Diamino-6-(2-pyridyl)-1,3,5-triazine Ligand

Anticancer Activity and DNA Binding of a Bifunctional Ru(II) Arene Aqua-Complex with the 2,4-Diamino-6-(2-pyridyl)-1,3,5-triazine Ligand

Efficient self-assembly of heterometallic triangular necklace with strong antibacterial activity

In vitro investigation of biophysical interactions between Ag(I) complexes of bis(methyl)(thia/selena)salen and ct‐DNA via multi‐spectroscopic, physicochemical and molecular docking methods along with cytotoxicity study

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