Ruthenium polypyridyl complexes and their modes of interaction with DNA: Is there a correlation between these interactions and the antitumor activity of the compounds?

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@article{b1b5052274ea4110af1b575bc1601b0b,
title = "Ruthenium polypyridyl complexes and their modes of interaction with DNA: Is there a correlation between these interactions and the antitumor activity of the compounds?",
abstract = "Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2]((2-n)+), and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}(2){mu-H2N(CH2)(6)NH2}](4+). The ligand tpy is 2,2':6',2aEuro(3)-terpyridine and the ligand L-1 is a bidentate ligand, namely, apy (2,2'-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L-2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L-2 were found to be able to coordinate to the DNA model base 9-ethylguanine by H-1 NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.",
keywords = "Linear dichroism, Cytotoxicity, DNA binding, Polypyridyl, Ruthenium",
author = "E Corral and ACG Hotze and {den Dulk}, H and Anna Leczkowska and A Rodger and Michael Hannon and J Reedijk",
year = "2009",
month = mar,
day = "1",
doi = "10.1007/s00775-008-0460-x",
language = "English",
volume = "14",
pages = "439--448",
journal = "Journal of Biological Inorganic Chemistry",
issn = "0949-8257",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Ruthenium polypyridyl complexes and their modes of interaction with DNA: Is there a correlation between these interactions and the antitumor activity of the compounds?

AU - Corral, E

AU - Hotze, ACG

AU - den Dulk, H

AU - Leczkowska, Anna

AU - Rodger, A

AU - Hannon, Michael

AU - Reedijk, J

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2]((2-n)+), and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}(2){mu-H2N(CH2)(6)NH2}](4+). The ligand tpy is 2,2':6',2aEuro(3)-terpyridine and the ligand L-1 is a bidentate ligand, namely, apy (2,2'-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L-2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L-2 were found to be able to coordinate to the DNA model base 9-ethylguanine by H-1 NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.

AB - Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2]((2-n)+), and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}(2){mu-H2N(CH2)(6)NH2}](4+). The ligand tpy is 2,2':6',2aEuro(3)-terpyridine and the ligand L-1 is a bidentate ligand, namely, apy (2,2'-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L-2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L-2 were found to be able to coordinate to the DNA model base 9-ethylguanine by H-1 NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.

KW - Linear dichroism

KW - Cytotoxicity

KW - DNA binding

KW - Polypyridyl

KW - Ruthenium

U2 - 10.1007/s00775-008-0460-x

DO - 10.1007/s00775-008-0460-x

M3 - Article

C2 - 19085018

VL - 14

SP - 439

EP - 448

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 0949-8257

IS - 3

ER -