NDLI: Interstrand DNA covalent binding of two dinuclear Ru(II) complexes. Influence of the extra ring of the bridging ligand on the DNA interaction and cytotoxic activity

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Leal, José M. Lozano, Héctor J. Platts, James A. García, Begoña Espino, Gustavo Carbayo, Arancha Busto, Natalia
Description	Author Affiliation: Lozano HJ ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.); Busto N ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.); Espino G ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.); Carbayo A ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.); Leal JM ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.); Platts JA ( School of Chemistry, University of Cardiff, Main Building, Park Place, CF10 3AT, Cardiff, UK.); García B ( Chemistry Deparment, University of Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain. begar@ubu.es.)
Abstract	In this work, we report experimental and computational evidence for the intercalation into the DNA base-pairs of the free quinones quinizarin (Q) and naphthazarin (N) and the interstrand covalent binding of their p-cymene di-ruthenium(II) complexes $(Cl_{2}Ru_{2}X,$ with X = N, Q bridging ligands). The intercalation extent for the N complex was larger than that for Q, which is in good agreement with the higher relative contour length and melting temperature for the same $C_{X}/C_{DNA}$ ratio and with the computational mean stacking distances between the ligand and the nearest base-pair (3.34 Å and 3.19 Å) for N and Q, respectively. However, the apparent binding constant of Q/DNA, two orders higher than that of N/DNA, indicates that the thermal stability of the X/DNA complex is more related to the degree of intercalation than to the magnitude of the binding constant. $Cl_{2}Ru_{2}X$ complexes undergo aquation, forming the aqua-derivatives $[(H_{2}O)_{2}Ru_{2}X]^{2+}.$ These can further bind covalently to DNA via interstrand crosslinking, through both Ru centres and two N7 sites of consecutive guanines, to give $(DNA_{1,2})Ru_{2}X$ complexes, by a mechanism similar to that of cisplatin. To the best of our knowledge, this type of interaction with dinuclear Ru(II) complexes has not been reported hitherto. The experimental and computational results reveal that the number of rings of the aromatic moiety and the covalent binding to DNA play a key role in the behaviour of the quinones and their Ru(II) derivatives. The cytotoxicity of the ligands and the corresponding Ru(II) complexes was evaluated in MCF-7, A2780, A2780cis tumour cells and in the healthy cell line MRC-5. The cytotoxic activity was notable for N and negligible for Q. The $IC_{50}$ values and the resistance (RF) and selectivity (SF) factors show that the $Cl_{2}Ru_{2}N$ complex is the most promising among the four studied anticancer drugs.
ISSN	14779226
Issue Number	11
Journal	Dalton Trans.
Volume Number	46
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2017-03-14
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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