Synthesis and antitumor activity of DNA binding cationic porphyrin-platinum(II) complexes

A new series of DNA binding 5,10,15-tri(N-methyl-4-pyridiniumyl)porphyrin (TrisMPyP)-platinum(II) conjugates was synthesized, in which different spacer ligands were used for appropriate coordination to platinum(II) complexes. Compound 9b exhibited in vivo antitumor activity (T/C%, 294) superior to cisplatin (T/C%, 184) against the leukemia L1210 cell line.     

Synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes containing a chiral tetradentate ligand

A series of novel dinuclear platinum(II) complexes with a chiral tetradentate ligand, (1R,1′R,2R,2′R)-N¹,N¹′-(1,2-phenylenebis(methylene))dicyclohexane-1,2-diamine (HL), and mono-carboxylic acid derivatives as ligands have been designed, synthesized, and characterized. In vitro cytotoxicity evaluation of synthesized complexes against human HepG-2, A549, HCT-116, and MCF-7 cancer cell lines has been conducted by MTT assays. All compounds showed antitumor activity to HepG-2 and HCT-116 cell lines. Compound L2 exhibited better cytotoxicity than that of carboplatin against HepG-2 and A549 cell lines and also showed comparable activity against HCT-116 cell line.     

Synthesis, characterization, DNA binding and cleavage studies of chiral Ru(II) salen complexes

Interaction of chiral Ru(II) salen complexes (S)-1 and (R)-1 with Calf Thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, CD measurements, thermal denaturation study and cleavage studies by agarose gel electrophoresis. The DNA binding affinity of (S)-1 (6.25 × 10³ M⁻¹) was found to be greater than (R)-1 (3.0 × 10³ M⁻¹). The antimicrobial studies of these complexes on five different gram (+)/(−) bacteria and three different fungal organisms showed selective inhibition of the growth of gram (+) bacteria and were not affective against gram (−) and fungal organisms. Further, the (S)-1 enantiomer inhibited the growth of organisms to a greater extent as compared to (R)-1 enantiomer.     

Synthesis,characterization and in vitro DNA binding studies of a new copper(II) complex containing antioxidant ferulic acid

A mononuclear Cu(II) complex, [Cu(FA)₂(NO₃)₂], in which FA is ferulic acid ((E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2-enoic acid), was synthesized and characterized by spectroscopic methods. The main structures of the ligand and its complexes with Cu²⁺ were optimized by QM calculations. The calculations on the structures of the [Cu(FA)₂(NO₃)₂] complexes forms and the intercalating with DNA profile were undertaken by UHF/PM6 and MMFF94 methods, respectively. In vitro studies (UV-vis spectroscopy, emission titration, circular dichroism techniques, and viscometry) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) showed that the complex interacts with calf-thymus DNA (ct-DNA) via an intercalative binding mode. The thermodynamic parameters, enthalpy change (ΔH), and entropy change (ΔS) showed that the acting forces between Cu(II) complex and ct-DNA mainly included van der Waals interactions and hydrogen bonds. Methylene blue (MB) displacement studies revealed that Cu(II) complex can substitute MB probe in the MB-DNA complex which was indicative of intercalative binding. The theoretical data confirm the experimental results with respect to the mechanism of binding.     

Copper(II) complexes containing hemilabile tridentate ligand as chromotropic probes

Two copper(II) complexes with the general formula [Cu(L)(H₂O)](ClO₄)₂ (1) and [Cu(L)₂](ClO₄)₂ (2), where L=3-((pyridin-2-ylmethyl)amino)propanamide, were synthesized and characterized by elemental analyses, IR, UV–vis spectroscopy techniques and molar conductance measurements. The crystal structures of the complexes were identified by single crystal X-ray diffraction analysis. The tridentate ligand L acts as an N₂O-donor through the nitrogen atoms of the pyridine and amine moieties as well the oxygen atom of the amide group. The copper(II) ions in both complexes have distorted octahedron structures so that the Cu(II) ion in 1 is coordinated by an aqua ligand and a tridentate ligand defining the basal plane, and by two oxygen atoms of the perchlorate ions occupying the axial positions. However, two ligands L are coordinated to the copper(II) ion in 2, where four nitrogen atoms of pyridine and amine groups occupy the equatorial positions and two oxygen atoms of the amide moieties exist in the apices. The chromotropism (halo-, solvato- and ionochromism) of both complexes were studied using visible absorption spectroscopy. The complexes are soluble in water and organic solvents and display reversible halochromism. The solvatochromism property is due to structural change followed by solvation of the vacant sites of the complexes. The complexes demonstrated obvious ionochromism and are highly sensitive and selective towards CN^? and N₃^? anions in the presence of other halide and pseudo-halide ions.     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

Synthesis,characterization, DNA binding studies and in vitro cytotoxicity of platinum(II)-dihalogenido complexes containing bidentate chelating N-donor ligands

Platinum(II) complexes, [Pt(L_x)X₂] (1–6), where X = Br or I and L_x = 2,2′-bipyridine or 1,10-phenanthroline derivatives (5,5′-dimethyl-2,2′-bipyridine (5-Mebpy), 4,4′-dimethyl-2,2′-bipyridine (4-Mebpy), and 5-amino-1,10-phenanthroline (5-NH₂phen)) were prepared. The complexes were characterized by the elemental analysis, mass spectrometry, infrared, and multinuclear (¹H, ¹³C and ¹⁹⁵Pt) 1-D and 2-D NMR spectroscopies, and by single-crystal X-ray analysis of [Pt(4-Mebpy)I₂] (4). All the platinum(II) complexes (1–6) were evaluated for in vitro cytotoxicity against human cancer cell lines A2780 and A2780R, and against non-malignant MRC5 cell line. All the complexes were nontoxic up to the 50 μM concentration, although they were found to readily bind to calf-thymus DNA (CT-DNA), as determined by spectrophotometric titration (K_b ≈ 10⁷ M^?1) and ethidium bromide displacement assay.     

Ferrocene-conjugated L-tryptophan copper(II) complexes of phenanthroline bases showing DNA photocleavage activity and cytotoxicity

Ferrocene-conjugated L-tryptophan (L-Trp) reduced Schiff base (Fc-TrpH) copper(II) complexes [Cu(Fc-Trp)(L)](ClO(4)) of phenanthroline bases (L), viz. 2,2'-bipyridine (bpy in 1), 1,10-phenanthroline (phen in 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 4), were prepared and characterized and their photocytotoxicity studied. Cationic reduced Schiff base (Ph-TrpH) complexes [Cu(Ph-Trp)(L)(H(2)O)](ClO(4)) (L = phen in 5; dppz in 6) having the ferrocenyl moiety replaced by a phenyl group and the Zn(II) analogue (7) of complex 4 were prepared and used as control species. The crystal structures of 1 and 5 with respective square-planar CuN(3)O and square-pyramidal CuN(3)O(2) coordination geometry show significantly different core structures. Complexes 1-4 exhibit a Cu(II)-Cu(I) redox couple near -0.1 V and the Fc(+)-Fc couple at ~0.5 V vs SCE in DMF-0.1 M [Bu(n)(4)N](ClO(4)) (Fc = ferrocenyl moiety). The complexes display a copper(II)-based d-d band near 600 nm and a Fc-centered band at ~450 nm in DMF-Tris-HCl buffer. The complexes are efficient binders to calf thymus DNA. They are synthetic chemical nucleases in the presence of thiol or H(2)O(2), forming hydroxyl radicals. The photoactive complexes are cleavers of pUC19 DNA in visible light, forming hydroxyl radicals. Complexes 2-6 show photocytotoxicity in HeLa cancer cells, giving IC(50) values of 4.7, 10.2, 1.3, 4.8, and 4.3 μM, respectively, in visible light with the appearance of apoptotic bodies. The complexes also show photocytotoxicity in MCF-7 cancer cells. Nuclear chromatin cleavage has been observed with acridine orange/ethidium bromide (AO/EB) dual staining with complex 4 in visible light. The complexes induce caspase-independent apoptosis in the HeLa cells.     

Synthesis,characterization and in vitro DNA binding studies of a new copper(II) complex containing an antiviral drug,valganciclovir

A new complex, [Cu(valcyte)₂(NO₃)₂], in which valcyte served as a valganciclovir drug, was synthesized and characterized by different physicochemical methods. Optimization of ligand structures and their complexes with Cu²⁺ were performed by semi-empirical and DFT methods. Binding interaction of this complex with calf-thymus DNA (ct-DNA) was explored by emission, absorption, circular dichroism and viscosity techniques. Additionally, cell line targeting was studied and cytotoxic effects of [Cu(valcyte)₂(NO₃)₂] (0.0–160 μg) on AGS and MCF-7 cell lines were reported. Percentage of Cell Viability and Apoptotic Index were assessed. The complex displayed significant binding properties to ct-DNA. Undertaking fluorometric studies, the binding mode of the complex with ct-DNA was explored utilizing Hoechst as a fluorescence probe, indicating the binding to be of groove mode. The DNA viscosity altered slightly in presence of the complex. Enthalpy and entropy changes during the interaction showed that the process is endothermic, with the complex mainly bound to ct-DNA by hydrophobic attraction. Values of ΔG revealed a spontaneous reaction between DNA and the complex. Optimized docked model of DNA–complex mixture confirmed the experimental results. The results of MMFF94 calculations indicated stability of [Cu(valcyte)₂(NO₃)₂] after docking with the modeled DNA profile, as compared to the DNA profile and valganciclovir results before the docking process. Cytotoxicity studies showed that an increase in [Cu(valcyte)₂(NO₃)₂] may result in a significant decrease in cell viability and increase apoptosis index in the treated cells, as compared to valganciclovir treated cells (p < 0.05). The findings further showed that [Cu(valcyte)₂(NO₃)₂] has potential for use in cancer therapy.     

Antimicrobial,anticancer and DNA binding studies of transition metal(II) complexes containing 2-phenyl-4-selenazole carboxylic acid

Science China Chemistry - Three novel transition metal complexes [ML2(phen)]·H2O (M= Mn, Co, Zn; HL= C10H7O2NSe, 2-phenyl-4-selenazole carboxylic acid, phen= 1,10-phenanthroline) 1～3...     

Synthesis,DNA binding and antitumor activities of some novel polymer–cobalt(III) complexes containing 1,10-phenanthroline ligand

The novel water-soluble polymer–cobalt(III) complex samples, cis-[Co(phen)₂(BPEI)Cl]Cl₂ · 4H₂O (phen = 1,10-phenanthroline, BPEI = branched polyethyleneimine), with different amounts of cobalt complex content in the polymer chain, were prepared by ligand substitution method in water–ethanol medium and characterized by Infra-red, UV–Vis, ¹H NMR spectral and elemental analysis methods. The interaction of these polymer–cobalt(III)-phenanthroline complex samples with calf thymus DNA has been explored using electronic absorption spectroscopy, emission spectroscopy and gel electrophoresis techniques. The presence of multiple small size molecular binding sites, namely, the cobalt(III)–phenanthroline complex moieties, and free amino groups in a single big sized polymer molecule enhanced both the electrostatic and/or van der Waals interaction and partial intercalative bindings with calf thymus DNA. The antitumor activity of a sample of polymer–cobalt(III) complex was determined using HEp-2 cell line and different cell death indicator stains and MTT assay. Many of the cultured HEp-2 cells treated with this complex suffered loss of viability and death mostly through apoptosis as evidenced by the nuclear and cytoplasmic morphology.     

DNA binding, nuclease activity and cytotoxicity studies of Cu(II) complexes of tridentate ligands

Cu(II) complexes of three tridentate ligands, L(1), L(2) and L(3), [L(1), N-((1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(2), N-((1-methyl-1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(3), 2-(pyridine-2-yl)-N-((pyridine-2-yl)methyl)ethanamine] respectively, were synthesized and characterized. The single crystal X-ray structure of complex 1 reveals the pseudo octahedral coordination geometry around the copper center. Absorption and fluorescence experimental evidence show good DNA binding propensity (in the order of 10(5) M(-1)) of the complexes. Thermal denaturation and circular dichroism (CD) analyses reveal minor structural changes of calf thymus (CT) DNA in presence of complexes and groove and/or surface binding of the complexes to CT-DNA. Kinetic DNA cleavage assay shows pseudo-first-order kinetic reaction between the complex and supercoiled (SC) DNA. In addition, mechanistic SC DNA cleavage results show higher DNA cleavage activity in presence of reducing agent, due to the presence of hydroxyl radicals. In vitro cytotoxicity assay of the complexes demonstrate that the complexes have low toxicity for different cancer cell lines and IC(50) values were between 37 and 156 μM.     

Phosphoester binding,DNA binding,DNA cleavage and in vitro cytotoxicity studies of simple heteroleptic copper(II) complexes with bidentate ligands

Abstract

Two mononuclear heteroleptic copper complexes, [Cu(±trans-dach)(bpy)](ClO₄)₂ 1a and [Cu(±trans-dach)(phen)](ClO₄)₂ 2a [dach?=?1,2-diaminocyclohexane, bpy?=?2,2′-bipyridine and phen?=?1,10-phenanthroline], were synthesized and analyzed by CHN analysis, electronic absorption, FT-IR spectroscopy, EPR, and SXRD. The molecular structures of 1a and 2a showed octahedral geometry around Cu(II). Both complexes interacted with phosphoesters and DNA. Their binding affinities with diphenylphosphate, di n-butylphosphate, trimethylphosphate, and triphenylphosphate were studied by UV–vis spectroscopy. For understanding the stereochemical role of dach ligand toward DNA interaction, enantiopure DACH complexes [Cu(R,R-trans-dach(bpy)](ClO₄)₂ 1b, [Cu(S,S-trans-dach)(bpy)](ClO₄)₂ 1c, [Cu(cis-dach)(bpy)](ClO₄)₂ 1d, [Cu(R,R-trans-dach)(phen)](ClO₄)₂ 2b, [Cu(S,S-trans-dach)(phen)](ClO₄)₂ 2c, and [Cu(cis-dach)(phen)](ClO₄)₂ 2d were synthesized and analyzed. All complexes interacted with calf thymus-DNA (CT-DNA) as studied by UV–vis spectroscopy. The nature of binding to CT-DNA was groove/electrostatic as supported by circular dichroism, cyclic voltammetry, and docking studies. Complexes were able to cleave plasmid DNA at 12.5 µM (1a–d) and 6 µM (2a–d), where 2d showed 64% Form II and 36% Form III. The in vitro cytotoxic studies of two different cancer cell lines showed inhibition with low IC₅₀ value in comparison to reference control (cisplatin). These complexes are efficient in inducing apoptosis in cancer cells, making them viable for potent anticancer activity.     

Synthesis,crystal structure,DNA/BSA interaction and in vitro antitumor activity of N-heterocycle Cu(II) and Co(II) complexes

Investigation of N-heterocycle transition metal complexes has led to the discovery of metal-based antitumor agents. Herein, two binuclear complexes, [Cu(p-4-bmb)(Ac)₂]₂ (1) and [Co(p-4-bmp)Cl₂]₂ (2), were prepared and characterized. The interactions of 1 and 2 with calf thymus (CT)-DNA and bovine serum albumin (BSA) were detected by absorbance and emission spectroscopy. The complexes bind to CT-DNA via an intercalative mode and show moderate affinity to BSA. Both complexes exhibited remarkable DNA cleavage activity. The MTT assay demonstrated that 1 exhibited higher cytotoxicity against three human alimentary system carcinoma cell lines compared to 2. Further, a cellular uptake assay demonstrated that 1 can accumulate in the nucleus and mitochondria of SMMC7721 cells to induce DNA damage and mitochondrial dysfunction. Fluorescence staining and flow cytometry analyses revealed that 1 can induce cell death by apoptosis. These findings should promote the development of benzimidazole-based transition metal complexes as novel chemotherapy agents with fewer side effects than conventional antitumor drugs.     

Acetonimine and 4-imino-2-methylpentan-2-amino platinum(II) complexes: synthesis and in vitro antitumor activity

The reaction of [Pt(dmba)(PPh3)Cl] [where dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl] with aqueous ammonia in acetone in the presence of AgClO4 gives the acetonimine complex [Pt(dmba)(PPh3)(NH=CMe2)]ClO4 (1). The reaction of [Pt(dmba)(DMSO)Cl] with aqueous ammonia in acetone in the presence of AgClO4 gives a mixture of [Pt(dmba)(NH=CMe2)2]ClO4 (2) and [Pt(dmba)(imam)]ClO4 (3a) (where imam = 4-imino-2-methylpentan-2-amino). [Pt(dmba)(DMSO)Cl] reacts with [Ag(NH=CMe2)2]ClO4 in a 1:1 molar ratio to give [Pt(dmba)(DMSO)(NH=CMe2)]ClO4 (4). The reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone at 70 degrees C in the presence of KOH gives [Pt(dmba)(CH2COMe)(NH=CMe2)] (5), whereas the reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone in the absence of KOH gives [Pt(dmba)(imam)]Cl (3b). The reaction of [NBu4]2[Pt2(C6F5)4(mu-Cl)2] with [Ag(NH=CMe2)2]ClO4 in a 1:2 molar ratio produces cis-[Pt(C6F5)2(NH=CMe2)2] (6). The crystal structures of 1 x 2 Me2CO, 2, 3a, 5, and 6 have been determined. Values of IC50 were calculated for the new platinum complexes against a panel of human tumor cell lines representative of ovarian (A2780 and A2780 cisR) and breast cancers (T47D). At 48 h incubation time complexes 1, 4, and 5 show very low resistance factors against an A2780 cell line which has acquired resistance to cisplatin. 1, 4, and 5 were more active than cisplatin in T47D (up to 30-fold in some cases). The DNA adduct formation of 1, 4, and 5 was followed by circular dichroism and electrophoretic mobility.     

DNA binding studies of new valine derived chiral complexes of tin(IV) and zirconium(IV)

Valine derived chiral complexes of SnCl4 (1) and ZrCl4 (2) were designed as potent antitumor agents. These complexes were characterized by elemental analysis, IR, 1H NMR, 119Sn NMR and ESI mass spectroscopy. In vitro binding studies of complexes 1 and 2 under physiological conditions at room temperature with CT-DNA were carried out employing UV-vis absorption titration, fluorescence studies and viscosity measurements. The extent of binding was quantified by Kb values of complexes 1 and 2 which were found to be 1.97×10(4) and 1.17×10(3) M(-1), respectively, suggesting that complex 1 has significantly greater DNA binding propensity in contrast to the complex 2. The mode of action at the molecular level was ascertained by the interaction of complex 1 with 5'GMP and 5'TMP which revealed that complex 1 binds via electrostatic mode with the oxygen of the negatively charged surface phosphate group of the DNA helix. The supercoiled pBR322 plasmid DNA cleavage activity of complex 1 was ascertained by gel electrophoresis assay.     

Synthesis and spectroscopic studies on complexes of N,N'-bis-(2-pyridinecarboxaldimine)-1,8-diaminonaphthalene (L); DNA binding studies on Cu(II) complex

The Schiff base ligand, N,N'-bis-(2-pyridinecarboxaldimine)-1,8-diaminonaphthalene (L), obtained by the condensation of 2-pyridinecarboxaldehyde and 1,8-diaminonaphthalene, has been used to synthesize the mononuclear complexes of the type [MLCl(2)] [M=Co(II), Ni(II), Cu(II) and Zn(II)]. The newly synthesized ligand (L) and its complexes have been characterized on the basis of results of elemental analysis, molar conductance, magnetic susceptibility measurements, Job's method and spectroscopic studies viz., FT-IR, Mass, (1)H and (13)C NMR. The UV-vis and magnetic moment data revealed an octahedral geometry around Co(II), Ni(II) and Cu(II) ions and conductivity data show a non-electrolytic nature of the complexes. Absorption and fluorescence spectroscopic studies support that Cu(II) complex exhibits significant binding to calf thymus DNA.     

Stabilization of G-quadruplex DNA, inhibition of telomerase activity and live cell imaging studies of chiral ruthenium(II) complexes

Telomerase inhibition is an attractive strategy for cancer chemotherapy. In the current study, we have synthesized and characterized two chiral ruthenium(II) complexes, namely, Λ-[Ru(phen)(2)(p-MOPIP)](2+) and Δ-[Ru(phen)(2)(p-MOPIP)](2+), where phen is 1,10-phenanthroline and p-MOPIP is 2-(4-methoxyphenyl)-imidazo[4,5f][1,10]phenanthroline. The chiral selectivity of the compounds and their ability to discriminate quadruplex DNA were investigated by using UV/Vis, fluorescence spectroscopy, circular dichroism spectroscopy, fluorescence resonance energy transfer melting assay, polymerase chain reaction stop assay and telomerase repeat amplification protocol. The results indicate that the two chiral compounds could induce and stabilize the formation of antiparallel G-quadruplexes of telomeric DNA in the presence or absence of metal cations. We report the remarkable ability of the two complexes Λ-[Ru(phen)(2)(p-MOPIP)](2+) and Δ-[Ru(phen)(2)(p-MOPIP)](2+) to stabilize selectively G-quadruplex DNA; the former is a better G-quadruplex binder than the latter. The anticancer activities of these complexes were evaluated by using the MTT assay. Interestingly, the antiproliferative activity of Λ-[Ru(phen)(2)(p-MOPIP)](2+) was higher than that of Δ-[Ru(phen)(2)(p-MOPIP)](2+), and Λ-[Ru(phen)(2)(p-MOPIP)](2+) showed a significant antitumor activity in HepG2 cells. The status of the nuclei in Λ/Δ-[Ru(phen)(2) (p-MOPIP)](2+)-treated HepG2 cells was investigated by using real-time living cell microscopy to determine the effects of Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+) on intracellular accumulation. The results show that Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+) can be taken up by HepG2 cells and can enter into the cytoplasm as well as accumulate in the nuclei; this suggests that the nuclei were the cellular targets of Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+).     

Copper(II) complexes with substituted thiosemicarbazones of alpha-ketoglutaric acid: synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity

New alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) derivatives and their copper complexes were synthesized and characterized by analytical and spectroscopic (IR and NMR) methods. For two of the ligands, Me-H(3)ct and Allyl-H(3)ct, and for a complex, [Cu(Me-Hct)(OH(2))](n) x 2nH(2)O, the X-ray structures were also determined. In the latter the copper atom shows a 4 + 1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the SNO tridentate ligand and the fourth by a carboxylic oxygen of an adjacent molecule that gives rise to a polymeric chain. DNA binding constants were determined, and studies of thermal denaturation profiles and nuclease activity were also performed. Tests in vitro on human leukemia cell line U937 were carried out on cell growth inhibition, cell cycle, and apoptosis induction.     

DNA binding and topoisomerase II inhibitory activity of water-soluble ruthenium(II) and rhodium(III) complexes

Water-soluble piano-stool arene ruthenium complexes based on 1-(4-cyanophenyl)imidazole (CPI) and 4-cyanopyridine (CNPy) with the formulas [(eta6-arene)RuCl2(L)] (L = CPI, eta6-arene = benzene (1), p-cymene (2), hexamethylbenzene (3); L = CNPy, eta6-arene = benzene (4), p-cymene (5), hexamethylbenzene (6)) have been prepared by our earlier methods. The molecular structure of [(eta6-C6Me6)RuCl2(CNPy)] (6) has been determined crystallographically. Analogous rhodium(III) complex [(eta5-C5Me5)RhCl2(CPI)] (7) has also been prepared and characterized. DNA interaction with the arene ruthenium complexes and the rhodium complex has been examined by spectroscopic and gel mobility shift assay; condensation of DNA and B-->Z transition have also been described. Arene ruthenium(II) and EPh3 (E = P, As)-containing arene ruthenium(II) complexes exhibited strong binding behavior, however, rhodium(III) complexes were found to be Topo II inhibitors with an inhibition percentage of 70% (7) and 30% (7a). Furthermore, arene ruthenium complexes containing polypyridyl ligands also act as mild Topo II inhibitors (10%, 3c and 40%, 3d) in contrast to their precursor complexes. Complexes 4-6 also show significant inhibition of beta-hematin/hemozoin formation activity.