Two new ligands maip (1) (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline), paip (2) (paip = 2-(4-aminophenyl)imidazo[4,5-f][1,10]phenanthroline), and their ruthenium (II) complexes [Ru(phen)2(maip)](ClO4)2 (3) and [Ru(phen)2(paip)](ClO4)2 (4) (phen = 1,10-phenanthroline) have been synthesized and characterized. The cytotoxicity of these compounds was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The apoptosis assay was carried out with acridine orange/ethidium bromide staining methods. The DNA-binding behaviors of complexes 3 and 4 were investigated by viscosity measurements, thermal denaturation, photocleavage, and spectroscopic methods. The results show that the two complexes intercalate into the base pairs of DNA. In the presence of a complex, apoptosis of BEL-7402 cells was observed. Experiments show that these compounds exhibit antioxidant activity against hydroxyl radicals.
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References
1.
ArockiasamyD.L., RadhikaS., ParthasarathiR., NairB.U.2009. Synthesis and DNA-binding studies of two ruthenium(II) complexes of an intercalating ligand. Eur J Med Chem, 44:2044–2051.
2.
BlasiusR., MoucheronC., MesmaskerA.K.2004. Photoadducts of metallic compounds with nucleic acids-role played by the photoelectron transfer process and by the TAP and HAT ligands in the RuII complexes. Eur J Inorg Chem, 20:3971–3979.
3.
CarterM.T., RodriguezM., BardA.1989. Voltammetric studies of the interaction of metal chelates with DNA. 2. Tris-chelated complexes of cobalt(III) and iron(II) with 1,10-phenanthroline and 2,2'-bipyridine. J Am Chem Soc, 111:8901–8911.
4.
ChairesJ.B., DattaguptaN., CrothersD.M.1982. Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: equilibrium binding studies on the interaction of daunomycin with deoxyribonucleic acid. Biochemistry, 21:3933–3940.
5.
ChenH., ParkinsonJ.A., MorrisR.E., SadlerP.J.2003. Highly selective binding of organometallic ruthenium ethylenediamine complexes to nucleic acids: novel recognition mechanisms. J Am Chem Soc, 125:173–186.
6.
ChenH.L., LiuH.Q., TzengB.C., YouY.S., PengS.M., YangM.S., CheC.M.2002. Syntheses of ruthenium(II) quinonediimine complexes of cyclam and characterization of their DNA-binding activities and cytotoxicity. Inorg Chem, 41:3161–3171.
7.
ChenL.M., LiuJ., ChenJ.C., TanC.P., ShiS., ZhengK.C., JiL.N.2008. Synthesis, characterization, DNA-binding and spectral properties of complexes [Ru(L)4(dppz)]2+ (L = Im and MeIm)J Inorg Biochem, 102:330–341.
8.
ChengC.C., RokitaS.E., BurrowsC.J.1993. Nickel(III)-promoted DNA cleavage with ambient dioxygen. Angew Chem Int Ed Engl, 32:277–280.
9.
CocchiettoM., SavaG.2000. Blood concentration and toxicity of the antimetastasis agent NAMI-A following repeated intravenous treatment in mice. Pharmacol Toxicol, 87:193–197.
10.
CohenG., EisenbergH.1969. Viscosity and sedimentation study of sonicated DNA-proflavine complexes. Biopolymers, 8:45–55.
11.
ErkkilaK.E., OdemD.T., BartonJ.K.1999. Recognition and reaction of metallointercalators with DNA. Chem Rev, 99:2777–2796.
12.
GaoF., ChaoH., WangJ.Q., YuanY.X., SunB., WeiY.F., PengB., JiL.N.2007. Targeting topoisomerase II with the chiral DNA-intercalating ruthenium(II) polypyridyl complexes. J Biol Inorg Chem, 12:1015–1027.
13.
HanM.J., GaoL.H., LüY.Y., WangK.Z.2006. Ruthenium(II) complex of Hbopip: synthesis, characterization, pH-induced luminescence off–on–off switch and avid binding to DNA. J Phys Chem B, 110:2364–2371.
14.
HartingerC.G., Zorbas-SeifriedS., JakupecM.A., ZorbasH., KepperB.K.2006. From bench to bedside–preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A)J Inorg Biochem, 100:891–904.
15.
HickmanJ.A.1992. Apoptosis induced by anticancer drugs. Cancer Metastasis Rev, 11:121–139.
16.
LeskoS.A., LorentzenR.J., Ts'oP.O.1980. Role of superoxide in deoxyribonucleic acid strand scission. Biochemistry, 19:3023–3028.
17.
LiT.R., YangZ.Y., WangB.D., QinD.D.2008. Synthesis, characterization, antioxidant activity and DNA-binding studies of two rare earth(III) complexes with naringenin-2-hydroxy benzoyl hydrazone ligand. Eur J Med Chem, 43:1688–1695.
18.
LiuJ., ZhengW.J., ShiS., TanC.P., ChenJ.C., ZhengK.C., JiL.N.2008. Synthesis, antitumor activity and structure–activity relationships of a series of Ru(II) complexes. J Inorg Biochem, 102:193–202.
19.
LiuY.J., ZengC.H., WuF.H., YaoJ.H., HeL.X., HuangH.L.2009. Synthesis, characterization, photocleavage of DNA and cytotoxicity of ruthenium(II) mixed-ligand complexes. J Mol Struc, 932:105–111.
20.
MarmurJ.1961. A procedure for the isolation of deoxyribonucleic acid from microorganism. J Mol Biol, 3:2080–2011.
21.
McGeeJ.D.1976. Theoretical calculations of the helix-coil transition of DNA in the presence of large, cooperatively binding ligands. Biopolymers, 15:1345–1375.
22.
MetcalfeC., ThomasJ.A.2003. Kinetically inert transition metal complexes that reversibly bind to DNA. Chem Soc Rev, 32:215–224.
23.
MosmannT.1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65:55–63.
24.
NilssonR., MerkelP.B., KearnsD.R.1972. Unambiguous evidence for the participation of singlet oxygen in photodynamic oxidadtion of amino acids. Photochem Photobiol, 16:117–124.
25.
ReichmannM.F., RiceS.A., ThomasC.A., DotyP.1954. A further examination of the molecular weight and size of desoxypentose nucleic acid. J Am Chem Soc, 76:3047–3053.
26.
SatyanarayanaS., DabrowiakJ.C., ChairesJ.B.1993. Tri(phenanthroline)ruthenium(II) enantiomer interactions with DNA: mode and specificity of binding. Biochemistry, 32:2573–2584.
27.
ShiS., LiuJ., LiJ., ZhengK.C., TanC.P., ChenL.N., JiL.N.2005. Electronic effect of different positions of the–NO2 group on the DNA-intercalator of chiral complexes [Ru(bpy)2L]2+(L = o-npip, m-npip and p-npip)Dalton Trans, 11:2038–2046.
28.
ShiS., XieT., YaoT.M., WangC.R., GengX.T., YangD.J., HanL.J., JiL.N.2009. Synthesis, characterization, DNA-binding and DNA-photocleavage studies of [Ru(bpy)2(pmip)]2+ and [Ru(phen)2(pmip)]2+ (pmip = 2-(2′-pyrimidyl)imidazo[4,5-f][1,10]phenanthroline. Polyhedron, 28:1355–1361.
29.
SpectorD.L, GoldmanR.D., LeinwandL.A.1998. Cells: A Laboratory Manual. Cold Spring Harbor Laboratory Press: New York. 1Chapter 15.
30.
SteckE.A., DayA.R.1943. Reactions of phenanthraquinone and retenequinone with aldehydes and ammonium acetate in acetic acid solution. J Am Chem Soc, 65:452–456.
SunJ., WuS., HanY., LiuJ., JiL.N., MaoZ.W.2008. Synthesis, crystal structure and DNA-binding studies of a Ru(II) complex containing two main ligands. Inorg Chem Commun, 11:1382–1384.
33.
SundquistW.I., LippardS.J.1990. The coordination chemistry of platinum anticancer drugs and related compounds with DNA. Coord Chem Rev, 100:293–322.
34.
TanC.P., LiuJ., LiH., ZhengW.J., ShiS., ChenL.M., JiL.N.2008. Synthesis, structural characteristics, DNA binding properties and cytotoxicity studies of a series of Ru(III) complexes. J Inorg Biochem, 102:1644–1653.
35.
WaringM.J.1965. Complex formation between ethidium bromide and nucleic acids. J Mol Biol, 13:269–282.
36.
WuJ.Z., LiL., YangG., ZengT.-X., JiL.N.1997. Characterization and luminiscent DNA-binding study of a series of ruthenium complexes containing 2-arylimidazo[f]1,10-phenanthroline. Polyhedron, 16:103–107.
37.
XiongY., JiL.N.1999. Synthesis, DNA-binding and DNA-mediated luminescence quenching of ruthenium(II) polypyridyl complexes. Coord Chem Rev, 185/186:711–733.
38.
YuH.J., HuangS.M., LiL.Y., JiaH.N., ChaoH., MaoZ.W., LiuJ.Z., JiL.N.2009. Synthesis, DNA-binding and photocleavage studies of ruthenium complexes [Ru(bpy)2(mitatp)]2+ and [Ru(bpy)2(nitatp)]2+J Inorg Biochem, 103:881–890.
39.
ZorzetS., SorceA., CasarsaC., CocchiettoM., SavaG.2001. Pharmacological effects of the ruthenium complex NAMI-A given orally to CBA mice with MCa mammary carcinoma. Met-Based drugs, 8:1–7.
