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Two new ruthenium(II) polypyridyl complexes [Ru(dmb)(2)(HECIP)](ClO(4))(2) (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(dmp)(2)(HECIP)](ClO(4))(2) (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 10(4) M(-1) (s = 1.62) and 2.97 (± 0.15) × 10(4) M(-1) (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed. Show less

A series of ruthenium complexes containing bis-benzimidazole derivatives have been synthesized and identified as able to target mitochondria and induce caspase-dependent apoptosis in cancer cells through superoxide overproduction. Show less

The cytostatic properties and cellular effects of novel diene-ruthenium(II) complexes of the types OC-6-13-[RuCl(2)(pp)(cod)] 1-5 (pp=2,2'-bipyridyl (bpy), phen=1,10-phenanthroline (phen), 5,6-dimethylphenanthroline (5,6-Me2phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), ethylenediamine (en)) and OC-6-24-[RuCl{(Me(2)N)(2)CS}(pp)(cod)](CF(3)SO(3)) 6-8 (pp=phen, 5,6-Me(2)phen, dpq) have been studied for the human cancer cell lines MCF-7 and HT-29 and for Jurkat leukemia cells. CD spectra indicate that 7 causes a massive distortion of the CT DNA B double helix toward the A form. Whereas the neutral complexes 1, 2 and 5 exhibit only modest antiproliferative activity toward MCF-7 and HT-29 cells, the monocationic complexes are significantly more active, in particular the DNA-distorting complex 7 with its IC(50) values of 0.73 and 0.42 μM, respectively. As established by online monitoring with a cell-based sensor chip, this potent 5,6-Me(2)phen complex invokes dose-dependent decreases in MCF-7 cellular respiration and extracellular acidification rates and causes a time-delayed decrease in the impedance of the cell layers, that can be ascribed to cell death. Treatment of Jurkat cells with 7 leads to high concentrations of reactive oxygen species and the induction of apoptosis. The pronounced dose-dependent inhibition of oxygen consumption by isolated mice mitochondria indicates the involvement of an intrinsic mitochondrial pathway in the programmed cell death process. Show less

The new monofunctional Ru(II)-arene complex [(η⁶-arene)Ru(II)(en)Cl]+, where en = 1,2-diaminoethane and the arene is para-terphenyl (complex 1) exhibits promising cytotoxic effects in human tumor cells including those resistant to conventional cisplatin (J. Med. Chem.2008, 51, 5310). The present study is focused on the cellular pharmacology of 1 to elucidate more deeply the mechanisms underlying its antitumor effects. We have identified several cellular mechanisms induced by 1 in human ovarian carcinoma cells, including inhibition of DNA synthesis, overexpression and activation of p53, expression of proapoptotic proteins p21(WAF1) and Bax, G₀/G₁ arrest, and nuclear fragmentation as a result of apoptotic, and, to a much lower extent, also necrotic processes. Thus, 1 inhibits growth of the cancer cells through induction of apoptotic cell death and G₀/G₁ cell cycle arrest. Further investigations have shown that 1 induces apoptosis by regulating the expression of Bcl-2 family proteins. There were significant differences in cellular responses to the treatment with 1 and with conventional cisplatin, particularly in the kinetics and the extent of these responses. In addition, the distinct p53 activation profile of 1 compared with cisplatin provides an explanation for the activity of this ruthenium drug against cisplatin-resistant cells. Hence complex 1 may provide an alternative therapy in patients with acquired cisplatin resistance, particularly with respect to its very low mutagenicity and different mode of action compared to platinum antitumor drugs in clinical use. Show less

Replacing the N,N-chelating ligand 2,2'-bipyridine (bpy) in the Ir(III) pentamethylcyclopentadienyl (Cp*) complex [(η(5)-C(5)Me(5))Ir(bpy)Cl](+) (1) with the C,N-chelating ligand 2-phenylpyridine (phpy) to give [(η(5)-C(5)Me(5))Ir(phpy)Cl] (2) switches on cytotoxicity toward A2780 human ovarian cancer cells (IC(50) values of >100 μM for 1 and 10.8 μM for 2). Ir-Cl hydrolysis is rapid for both complexes (hydrolysis equilibrium reached in <5 min at 278 K). Complex 2 forms adducts with both 9-ethylguanine (9-EtG) and 9-methyladenine (9-MeA), but preferentially with 9-EtG when in competition (ca. 85% of total Ir after 24 h). The X-ray crystal structure of [(η(5)-C(5)Me(5))Ir(phpy)(9-EtG-N7)]NO(3)·1.5CH(2)Cl(2) confirms N7 binding to guanine. Two-dimensional NMR spectra show that complex 2 binds to adenine mainly through N1, consistent with density functional theory (DFT) calculations. DFT calculations indicate an interaction between the nitrogen of the NH(2) group (9-MeA) and carbons from phpy in the adenine adduct of complex 2. Calculations show that the most stable geometry of the adduct [(η(5)-C(5)Me(5))Ir(phpy)(9-EtG-N7)](+) (3b) has the C6O of 9-EtG orientated toward the pyridine ring of phpy, and for [(η(5)-C(5)Me(5))Ir(phpy)(9-MeA-N1)](+) (4(N1)a), the NH(2) group of 9-EtA is adjacent to the phenyl ring side of phpy. Complex 2 is more hydrophobic than complex 1, with log P values of 1.57 and -0.95, respectively. The strong nucleobase binding and high hydrophobicity of complex 2 probably contribute to its promising anticancer activity. Show less

We present the synthesis, characterization, and photophysical properties of three luminescent rhenium(I) polypyridine fluorous complexes [Re(Me(2)bpy)(CO)(3)(L)](PF(6)) (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine; L = 3-amino-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NH(2)) (1), 3-isothiocyanato-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NCS) (2), 3-ethylthioureidyl-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-TU-C(2)H(5)) (3)). The isothiocyanate complex 2 has been used to label bovine serum albumin (BSA) and glutathione (GSH). The photophysical properties of the resultant bioconjugates have been studied. The isolation of the luminescent fluorous rhenium-GSH conjugate from a mixture of 20 amino acids has been demonstrated using fluorous solid-phase extraction (FSPE). Additionally, the cytotoxicity of complexes 1 and 3 toward HeLa cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular uptake properties of complex 3 have also been investigated by laser-scanning confocal microscopy. Show less

A new ligand and two ruthenium(II) complexes [Ru(bpy)(2)(DNPIP)](ClO(4))(2)1 and [Ru(bpy)(2)(DAPIP)](ClO(4))(2)2 were synthesized and characterized. The DNA-binding constants for complexes 1 and 2 were determined to be 2.24 (±0.30) × 10(5) M(-1) (s = 1.29) and 6.34 (±0.32) × 10(4) M(-1) (s = 2.84). The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 were assessed against three tumor cell lines. The apoptosis and cellular uptake were studied. The retardation assay of pGL 3 plasmid DNA was explored. The cell cycle arrest was analysized by flow cytometry. The antioxidant activities of the ligand and complexes were also investigated. Show less

A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)(2)H][trans-RuCl(4)(DMSO)(2)] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl(4)(DMSO)(n-Cl-LH)]⋅xSol (1-3), trans-[RuCl(4)(DMSO)(n-Br-LH)]·xSol (4-6), trans-[RuCl(4)(DMSO)(n-OMe-LH)]·xSol (7-9) and trans-[RuCl(4)(DMSO)(n-OH-LH)]·xSol (10-12); n=2, 3, and 4, x=0-1.5; and Sol = H(2)O, DMSO, EtOH and/or (Me)(2)CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES+(positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl(4)(DMSO)(3-Br-LH)]⋅(Me)(2)CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC(50)>100μM in contrast to the moderate results regarding the antiradical activity with IC(50)≈10(-3)M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ. Show less

Two new ruthenium(II) complexes, [Ru(phen)2(DNPIP)](ClO4)2 (1) and [Ru(phen)2(DAPIP)](ClO4)2 (2), were synthesized and characterized. The DNA-binding properties of these complexes were investigated using UV/vis absorption titration, viscosity measurements, thermal denaturation, and photoactivated cleavage. The DNA binding constants for complexes 1 and 2 are 2.63 ± 0.25×10(5) M(-1) (s=2.45) and 1.51±0.18×10(5) M(-1) (s=1.34). The results indicated that these complexes interacted with DNA through the intercalative mode. The cytotoxicity in vitro of complexes 1 and 2 were assessed against BEL-7402, HepG-2, and MCF-7 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was studied with the acridine orange/ethidium bromide staining method. The antiproliferative mechanism was explored with flow cytometry. Cellular uptake studies showed that complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Cell cycle arrest and antioxidant activity were also investigated. Show less

The Ru(II) complex fac-[RuCl(dmso-S)(3)(dmso-O)(2)][PF(6)] (P2) was found to be an excellent precursor for the facile preparation in high yield of half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N)(2)][PF(6)] (e.g. (N)(2) = 1,2-diaminoethane (en, 4), trans-1,2-diaminocyclohexane (dach, 5), or 2 NH(3) (6)). Neutral half sandwich-type compounds of the general formula fac-[RuCl(dmso-S)(3)(N-O)] where N-O is an anionic chelating ligand (e.g. N-O = picolinate (pic, 7)) are best prepared from the universal Ru(II)-dmso precursor cis-[RuCl(2)(dmso)(4)] (P1). These complexes, that were fully characterized in solution and in the solid state, are structurally similar to the anticancer organometallic compounds [Ru(η(6)-arene)(chel)Cl][PF(6)](n) but, in place of a face-capping arene, have the fac-Ru(dmso-S)(3) fragment. In contrast to what observed for the corresponding arene compounds, that rapidly hydrolyze the Cl ligand upon dissolution in water, compounds 4-6 are very stable and inert in aqueous solution. Probably their inertness is the reason why they showed no significant cytotoxicity against the MDA-MB-231 cancer cell line. Show less

The cytostatic properties of novel rhodium(III) thiacrown ether complexes [RhCl(LL)([9]aneS(3))](n+) with either aromatic κ(2)N ligands (n = 2) or anionic chelate ligands (n = 1) have been investigated for the human cancer cell lines HT-29 and MCF-7 and for immortalized HEK-293 cells. Taken together with literature IC(50) values for analogous complexes with polypyridyl ligands or 1,4-dithiane, the in vitro assays indicate that dicationic complexes with soft κ(2)N (imino) or κ(2)S (thiaether) ligands exhibit significantly higher antiproliferative effects than those with hard κ(2)N (amino) ligands. Dicationic complexes are more active than monocationic complexes with similar ligands. Pronounced apoptosis-inducing properties towards Jurkat cells were established for complexes with LL = bpm, dpq, and 1,4-dithiane. The order of activity (bpm > 1,4-dithiane > dpq > bpy) contrasts to that observed for adhesive cancer cells (bpm > bpy, 1,4-dithiane > dpq). Necrosis is insignificant in all cases. The percentage of Jurkat cells exhibiting apoptosis after 24 or 48 h incubation periods is directly correlated to the percentage of cells exhibiting high levels of reactive oxygen species. As established by online monitoring with a sensor chip system, treatment of MCF-7 cells with the bpm and 1,4-dithiane complexes leads to a significant and permanent concentration-dependent decrease in oxygen consumption and cellular adhesion. Show less

Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50): 1.0-20.2 μM), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds. Show less

Three novel Ru(II) complexes of the general formula [Ru(N-N)(2)(Norharman)(2)](SO(3)CF(3))(2), where N-N = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), 4,7-diphenyl-1,10-phenanthroline (DIP, 3) and Norharman (9H-pyrido[3,4-b]indole) is a naturally occurring β-carboline alkaloid, have been synthesized and characterized. The molecular structures of 1 and 2 have been determined by X-ray diffraction analysis. The cellular uptake efficiencies, in vitro cytotoxicities and apoptosis-inducing properties of these complexes have been extensively explored. Notably, 1-3 exhibit potent antiproliferative activities against a panel of human cancer cell lines with IC(50) values lower than those of cisplatin. Further studies show that 1-3 can cause cell cycle arrest in the G0/G1 phase and induce apoptosis through mitochondrial dysfunction and reactive oxygen species (ROS) generation. In vitro DNA binding studies have also been conducted to provide information about the possible mechanism of action. Show less

In our previous study, ruthenium(II)-p-cymene complexes of general formula [(η(6)-p-cymene)Ru(L)Cl2], L: 3-acetylpyridine (1), 2-amino-5-chloropyridine (2); and [(η(6)-p-cymene)Ru(HL)Cl], HL: 2,3-pyridinedicarboxylic acid (3), 2,4-pyridinedicarboxylic acid (4), revealed low antiproliferative activity, except complex [(η(6)-p-cymene)RuCl(picolinic acid)]·H(2)O (5) which exhibited IC(50) around 80 μM. In this study we further investigated in vitro potential of antimetastatic action of ruthenium complexes on HeLa and two endothelial cell lines. Comparison of structure and activity of five complexes indicated heterogenic mode of activity, with regard to the potential of antimetastatic and antiproliferative effect. Replacement of substituted pyridine ligand with picolinic acid (complex 5) around Ru(II) center contributed to complex cytotoxicity and ruthenium DNA binding affinity. Analysis of ruthenium(II) accumulation in DNA and protein fractions of HeLa cells, using ICP-OES revealed significantly higher content of complex 5 in DNA fraction in comparison to the other tested compounds. It also altered cell cycle progression, affected expression of DNA repair enzymes ERCC1 and MSH2, and showed enhanced activity in combination with 3-aminobenzamide. Regardless of their effect on cell growth, Ru(II) complexes exerted antimetastatic effect on several tumor cell lines in vitro, achieved mostly by the effect on cell adhesion, migration and angiogenesis, while picolinate ruthenium(II)-arene additionally exerted inhibitory effect on extracellular matrix degradation. Show less

Two ruthenium (II) complexes [Ru(dmb)2(APIP)](ClO4)2 (APIP=2-(2-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline, dmb=4,4'-dimethyl-2,2'-bipyridine; 1) and [Ru(dmb)2(HAPIP)](ClO4)2 (HAPIP=2-(2-hydroxyl-4-aminophenyl)imidazo[4,5-f ][1,10]phenanthroline; 2) were synthesized and characterized. DNA binding was investigated by electronic absorption titration, luminescence spectra, thermal denaturation, viscosity measurements, and photocleavage. The DNA binding constants for complexes 1 and 2 were 4.20 (±0.14)×10(4) and 5.45 (±0.15)×10(4) M(-1). The results suggest that these complexes partially intercalate between the base pairs. The cytotoxicity of complexes 1 and 2 was evaluated by MTT assay. Cellular uptake was observed under fluorescence microscopy; complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Apoptosis and the antioxidant activity against hydroxyl radicals (•OH) were also explored. Show less

We have synthesized and evaluated the biological properties of a compound of the type [η(6)-p-cymene)Ru(EtATSC)Cl]Cl (1) where EtATSC = 2-anthracen-9-ylmethylene-N-ethylhydrazinecarbothioamide, a thiosemicarbazone. The complex has been characterized by elemental analysis, spectroscopically (NMR, UV-Vis, and IR) and structurally by XRD. The in vitro anticancer activity of 1 has been evaluated against two human colon cancer cell lines. The IC(50) value for activity against HCT-116 was 224 ± 7 μM and 205 ± 5 μM against the Caco-2 cell line. The proficiency of 1 as an antibacterial agent was also evaluated against six bacterial strains. The minimum inhibitory concentration for Bacillus cereus was determined to be 5 μM and for Enterococcus faecalis it was 20 μM. At the maximum concentration tested the complex showed no activity against the Gram-negative strains. The complex binds strongly to human serum albumin with a binding constant of 1.37 ± 0.02 M(-1) at 308 K on a single binding site. It is also a strong binder to DNA with an apparent binding constant of 2.82 × 10(5) M(-1) at 308 K. 1 shows very good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 μM. Show less

The antiproliferative properties and cellular impact of novel substitutionally inert rhodium(III) complexes of the types [Rh{(CH₃)₂ NCS₂}₂(pp)]Cl 3-5 (pp=5,6-Me₂phen, dpq, dppz) and OC-6-23-[Rh(2-S-py)₂(pp)]Cl 6 and 7 (2-S-py=pyridine-2-thiolate; pp=dpq, dppz) have been investigated for the adherent human cancer cell lines MCF-7 and HT-29 and for non-adherent Jurkat cells. Whereas CD and viscosity measurements indicate that the polypyridyl ligands of 4 and 5 intercalate into CT DNA, this is not the case for the analogous pyridine-2-thiolate complexes 6 and 7. Complexes 3-7 all exhibit a high antiproliferative activity towards MCF-7 and HT-29 cells, with IC(50) values in the range 0.055-0.285 μM. As established by online monitoring with a cell-based sensor chip, the highly cytostatic complex 6 (IC(50)=0.059 and 0.078 μM) invokes an immediate concentration-dependent reduction of MCF-7 cell respiration and a time-delayed decrease in cellular impedance, which can be ascribed to the induction of cell death. Annexin V/PI assays demonstrated that 6 also has a pronounced antiproliferative activity towards Jurkat cells and that it invokes extensive apoptosis and high concentrations of reactive oxygen species in these leukemia cells. The observation of a dose-dependent inhibition of the oxygen consumption of isolated mice mitochondria indicates the involvement of an intrinsic mitochondrial pathway in this process. Show less

Ruthenium(II) methylimidazole complexes, with the general formula [Ru(MeIm)(4)(N⌢N)](2+) (N⌢N = tip (RMC1), iip (RMC2), dppz (RMC3), dpq (RMC4); MeIm = 1-methylimidazole, tip = 2-(thiophene-2-yl)-1H-imidazo [4,5-f] [1,10]phenanthroline, iip = 2-(1H-imidazol-4-yl)-1H-imidazo [4,5-f] [1,10]phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, dpq = pyrazino [2,3-f] [1,10]phenanthroline), were synthesized and characterized. As determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, these complexes displayed potent anti-proliferation activity against various cancer cells. RMC1 inhibited the growth of A549 (human lung adenocarcinoma) lung cells through induction of apoptotic cell death, as evidenced by the accumulation of cell population in sub-G1 phase. RMC1 also induced the depletion of mitochondrial membrane potential in A549 cells by regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Another experiment showed that Bid protein was also activated by RMC1, which implied that RMC1 could existed two pathways crosstalk, namely, have exogenous death receptor signaling pathway. These results demonstrated that RMC1 induced cancer cell death by acting on both mitochondrial and death receptor apoptotic pathways, suggesting that RMC1 could be a candidate for further evaluation as a chemotherapeutic agent against human cancers. Show less

A library of 32 organoruthenium compounds has been synthesised. Known and novel C-N cyclometalated compounds as well as N-C-N and N-N-C pincer derivatives of this metal have been used in this purpose. Most of the compounds have been tested for their in vitro antitumoral behaviours, good to excellent activities have thus been found. Several of the newly synthesized compounds pass the symbolic barrier of the nanomolar range for their IC(50) indicating a critical improvement. The level of activity is tentatively correlated to physicochemical properties of the compounds such as their Ru(III/II) redox potential and their lipophilicity (log P). Show less

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)(2)Ru(TSC)](PF(6))(2) (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2'-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV-Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10(4) M(-1). They are also strong binders of human serum albumin having binding constants on the order of 10(4) M(-1). The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC(50) values range from 7 - 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC(50) values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II. Show less

Two ruthenium(II) complexes [Ru(bpy)(2)(bfipH)](2+) (1) and [Ru(phen)(2)(bfipH)](2+) (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that the two complexes bind to DNA in an intercalative mode. Complexes 1 and 2 can efficiently photocleave pBR322 DNA in vitro under irradiation, singlet oxygen ((1)O(2)) was proved to contribute to the DNA photocleavage process. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru(II) complexes acted as efficient dual inhibitors of topoisomerases I and II. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. The AO/EB staining assay indicated that Ru(II) complexes could induce the apoptosis of HeLa cells. Show less