Heteroscorpionate‐based heteroleptic copper(II) complexes: Antioxidant,molecular docking and in vitro cytotoxicity studies

Three new heteroscorpionate ligands, (2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL¹), (4‐diethylamino‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL²) and (5‐bromo‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL³), and their heteroleptic copper(II) complexes of the type [Cu(L^1–3)diimine]ClO₄ ( 1 – 6 ; where diimine =2,2′‐bipyridyl or 1,10‐phenanthroline) have been synthesized and characterized using spectroscopic methods. The molecular structure of ligand HL¹ was determined by single‐crystal X‐ray diffraction. UV–visible, electron paramagnetic resonance and theoretical studies suggest a distorted square pyramidal geometry around copper(II) ion. Analyses of highest occupied and lowest unoccupied molecular orbitals have been used to explain the charge transfer taking place within the complexes. The antioxidant activities of the heteroscorpionate ligands and their heteroleptic copper(II) complexes were determined using ABTS, DPPH and H₂O₂ free radical scavenging assays with respect to standard antioxidant ascorbic acid. In molecular docking studies, the complexes showed π–π, hydrogen bonding, van der Waals and electrostatic interactions with fibroblast growth factor receptor kinase. In vitro cytotoxicity activities of ligands and copper(II) complexes were examined on human breast adenocarcinoma (MCF‐7), cervical (HeLa) and lung (A549) cancer cell lines and normal human dermal fibroblast cell line using MTT assay. Complex 4 exhibited higher anticancer activity than the other complexes against all three cancer lines, being more potent than the standard drug cisplatin.     

Three new mixed‐ligand copper(II) complexes containing glycyl‐l‐valine and N,N‐aromatic heterocyclic compounds: Synthesis,characterization, DNA interaction,cytotoxicity and antimicrobial activity

Three novel copper(II) complexes, [Cu(Gly‐l ‐Val)(HPBM)(H₂O)]·ClO₄·H₂O ( 1 ), [Cu(Gly‐l ‐Val)(TBZ)(H₂O)]·ClO₄ ( 2 ) and [Cu(Gly‐l ‐Val)(PBO)(H₂O)]·ClO₄ ( 3 ) (Gly‐l ‐Val = glycyl‐l ‐valine anion, HPBM = 5‐methyl‐2‐(2′‐pyridyl)benzimidazole, TBZ = 2‐(4′‐thiazolyl)benzimidazole, PBO = 2‐(2′‐pyridyl)benzoxazole), have been prepared and characterized with elemental analyses, conductivity measurements as well as various spectroscopic techniques. The interactions of these copper complexes with calf thymus DNA were explored using UV–visible, fluorescence, circular dichroism, thermal denaturation, viscosity and docking analyses methods. The experimental results showed that all three complexes could bind to DNA via an intercalative mode. Moreover, the cytotoxic effects were evaluated using the MTT method, and the antimicrobial activity of these complexes was tested against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The results showed that the activities are consistent with their DNA binding abilities, following the order of 1 > 2 > 3 .     

Synthesis,structure elucidation,DNA binding and molecular docking studies of novel copper(II) complexes of two 1,3,4-thiadiazolethiosemicarbazone derivatives

Four novel Cu(II) chelates were synthesized by reacting hydrated CuCl₂ and Cu(CH₃COO)₂ with two derivatives of 1,3,4-thiadiazolethiosemicarbazone. The structures and geometries of the synthesized complexes were deduced applying the alternative analytical and spectral tools confirming the complexes to have the formulae [(LH)Cu(Cl)]•0.5H₂O, [(LH)Cu(OAc)(H₂O)₂]•0.5H₂O, [(LCl)Cu(Cl)(H₂O)₂]•H₂O and [(LCl)Cu(OAc)]; where LH and LCl are phenyl and p-chlorophenyl derivatives of 1,3,4-thiadiazolethiosemicarbazone ligands, respectively (deprotonated form). IR spectral data confirmed the coordination of the ligands to the copper center as monobasic tridentate in the thiol form. Thermal analysis, UV–Vis spectra and magnetic moment assured the geometry around the copper center to be square planar, trigonal bipyramid and octahedral which have been confirmed by the computational studies. The two ligand derivatives and their copper complexes were applied to evaluate their binding modes with SS-DNA via UV–Vis spectral titration and viscosity measurements. The DNA-binding constant (k_b) values of the investigated derivatives were calculated and compared with ethidium bromide in order to assess their mode of binding with DNA. Moreover, docking study of these complexes was carried out to recognize the drug–DNA interactions and to calculate their binding energies.     

Synthesis,characterization and biological applications of new copper(II) complexes of aryl hydrazones

On treatment of copper(II) acetate with aryl hydrazone ligands, four new solid derivatives of copper(II) were produced in appreciable yields. Various characterization techniques including infrared, UV–visible, NMR, electron paramagnetic resonance and mass spectroscopies, elemental analysis, scanning electron microscopy, powder X‐ray diffraction and thermogravimetric analysis revealed a tetra‐coordination in all the mononuclear crystalline complexes with high thermal stability. Further, significant interaction of these novel complexes with calf thymus DNA via intercalative mode of binding was revealed by electronic absorption spectroscopy. The chemical nuclease activity of the complexes on pBR322 DNA was investigated in the presence and absence of oxidizing agent (H₂O₂). A potent nuclease activity was observed only in the presence of H₂O₂. Further, antibacterial and antifungal studies of the new ligands and complexes revealed that the latter possessed comparatively better activity.     

Biological contour,molecular docking and antiproliferative studies of DNA targeted histidine based transition metal(II) complexes: Invention and its depiction

A novel series of histidine derived transition metal complexes were synthesized and characterized by multispectral techniques such as UV‐Vis., FT IR, EPR, NMR, ESI‐mass analysis and other physico‐chemical methods like elemental analysis, molar conductivity, magnetic susceptibility. The synthesized compounds were attempted for their biological prospective. The biological studies involved are DNA interaction (binding and damage), antimicrobial, antioxidant, antiproliferative and molecular docking. DNA interaction studies were carried out with the help of UV‐Vis absorption titration, viscosity measurement and cyclic voltammetric techniques which revealed that the synthesized compounds could interact with CT‐DNA through intercalative binding mode. A gel electrophoresis assay demonstrated the ability of complexes to cleave the supercoiled pUC18 DNA. The antioxidant property shows that the metal complexes have preferable ability to scavenge hydroxyl radical than the ligand. Moreover, the antimicrobial assay indicates that these complexes are good antimicrobial agents against various pathogens. Furthermore, the in vitro antiproliferative activities of the complexes were examined on HeLa, Hep G2 and NIH 3 T3 cell lines using an MTT assay. The morphological changes were investigated using Hoechst 33258 staining apoptosis assay. In addition, molecular docking studies were executed to considerate the nature of binding of the synthesized complexes with protein and DNA.     

Synthesis,characterization, antimicrobial activity, 3D-QSAR,DFT, and molecular docking of some ciprofloxacin derivatives and their copper(II) complexes

Six new derivatives of ciprofloxacin compounds and their copper(II) complexes were synthesized, characterized by spectroscopic methods (ultraviolet–visible [UV–vis], Fourier transform infrared [FTIR], nuclear magnetic resonance [NMR], mass spectrometry [MS], and electron paramagnetic resonance [EPR]), and tested for antibacterial activities against gram-negative and gram-positive bacteria. The data showed that ciprofloxacin derivatives act as bidentate ligands and the metal ions coordinate through the pyridone carbonyl and the carboxylate oxygen atoms. Tetragonally distorted octahedral ligand fields were assumed for all complexes based on their spectral studies. Copper(II) complexes of the synthesized ciprofloxacin derivatives revealed higher antibacterial activities against gram-positive and gram-negative bacterial species than the parent ciprofloxacin antibiotic. Furthermore, three-dimensional quantitative structure–activity relationship (3D-QSAR) models were evaluated by studying 30 antibiotic compounds of the quinolone class. Density function theory (DFT) calculations were applied to evaluate the optimized geometrical structures using the B3LYP method and 6-311G(d,p) basis set. The 3D-QSAR study revealed that there are eight optimum parameters that give the best predictive modulation with good reliability (R² = 0.996, F = 12.004, sigma = 0.426). In silico molecular docking was also performed on the derivatives, and the results revealed the presence of two types of interactions between the Escherichia coli and the derivatives, H-bonding and Van der Waals interactions, and an effective inhibition at the docked site.     

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.     

Copper(II) complexes of acylhydrazones: synthesis,characterization and DNA interaction

Two new acylhydrazone copper(II) complexes of 4‐hydroxy‐N′‐[(1E)‐1‐(4‐methylphenyl)ethylidene]benzohydrazide (HL¹) and 4 ethyl [4‐({(2E)‐2‐[1‐(4‐methylphenyl)ethylidene]hydrazinyl}carbonyl)phenoxy]acetate (HL²) have been synthesized and characterized. The structures of both acylhydrazone and copper(II) complexes were identified by elemental analysis, infrared spectra, UV–visible electronic absorption spectra, magnetic susceptibility measurements, TGA and powder X‐ray diffraction. DNA binding and DNA cleavage activities of the synthesized copper complexes were examined by using UV‐visible titration and agarose gel electrophoresis, respectively. The effect of complex concentration on the DNA cleavage reactions in the absence and presence of H₂O₂ was also investigated. The results indicate that all the complexes bind slightly to calf thymus DNA and cleavage pBR322 DNA. The mechanistic studies demonstrate that a hydrogen peroxide‐derived species and singlet oxygen (¹O₂) are the active oxidative species for DNA cleavage. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,characterization, DNA binding,apoptosis and molecular docking of three Mn(II), Zn(II) and Cu(II) complexes with terpyridine‐based carboxylic acid

A series of novel cytotoxic compounds, [Mn(cpt)₂], [Zn(tpt)(H₂O)₂]?DMA?2(H₂O) and [Cu(tpt)]?DMA (cpt = 4′‐(4‐carboxyphenyl)‐2,2′:6′,2″‐terpyridine, tpt = 4‐(2,4,6‐tricarboxylphenyl)‐2,2′:6′,2″‐terpyridine, DMA = (CH₃)₂NH), were isolated and characterized. The structures of these complexes were characterized using single‐crystal X‐ray diffraction. The mode and extent of binding between fish sperm DNA and the complexes were investigated using fluorescence spectroscopy and molecular docking. These results indicate the ability of the complexes to bind to DNA with different binding affinities. The binding of the Zn(II) complex with DNA is stronger than that of the corresponding Cu(II) analogue, which is expected due to the z* effect and geometry. The ability of these complexes to cleave pBR322 plasmid DNA was demonstrated using gel electrophoresis assay, showing that the complexes have effective DNA cleavage activity. In addition, the cytotoxic effects of these complexes were examined on HeLa cells (human cervix epithelia carcinoma cells) in vitro. The three complexes exhibit different cytotoxic effects and decent cancer cell inhibitory rate. This means that the structures and type of metal have a great influence on the activity of these novel complexes.     

Five new cobalt(II) complexes based on indazole derivatives: synthesis,DNA binding and molecular docking study

Five cobalt(II) complexes based on 1H-indazole-3-carboxylic acid (H₂L), [Co(phen)(HL)₂]·2H₂O (1), [Co(5,5′-dimethyl-2,2′-bipy)(HL)₂] (2), [Co(2,2′-bipy)₂(HL)₂]·5H₂O (3), [Co₂(2,9-dimethyl-1,10-phen)₂(L)₂] (4) and [Co₂(6,6′-dimethyl-2,2′-bipy)₂(L)₂]·H₂O (5) (2,2'-bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline), have been synthesized and structurally characterized by elemental analyses, IR and UV-vis spectroscopies and single-crystal X-ray crystallography. The results indicate that 1–3 possess mononuclear Co(II) structures, while 4 and 5 exhibit binuclear structure. 1D water tape which is linked by the multiple hydrogen bonds was embedded in the 3D motif of complex 3. Complexes 4 and 5 show two orthogonal planes of motif that was constituted by phen/2,2′-bipy and indazole acid, respectively. The intermolecular interactions including hydrogen bonding and π-π stacking interactions are stabilizing these complexes. The interactions of the synthesized complexes with calf-thymus DNA (CT-DNA) have been investigated by UV-vis absorption titration, ethidium bromide displacement assay and viscosity measurements. The results reveal that the complexes could interact with CT-DNA via a groove binding mode. Their behavior rationalization was further theoretically studied by molecular docking.     

Synthesis,urease inhibitory activities,and molecular docking studies of two Cu(II) complexes

Two mononuclear copper(II) complexes, [Cu(C₄H₃N₂O₂)₂?·?4H₂O] (1) and [Cu(C₁₂H₁₁N₂O₂Cl₂)₂] (2), were synthesized and structurally characterized by single-crystal X-ray analysis. The copper(II) adopts a square-planar environment in 1, while the geometry in 2 can be described as distorted square-pyramidal. Complexes 1 and 2 were evaluated for their inhibitory activities against jack bean urease in vitro and both were found to have strong inhibitory activities comparable to that of acetohydroxamic acid. A docking simulation was performed to position 2 into the jack bean urease active site to determine the probable binding conformation.     

Synthesis and structural and DNA binding studies of mono‐ and dinuclear copper(II) complexes constructed with ─O and ─N donor ligands: Potential anti‐skin cancer drugs

Mononuclear and dinuclear copper(II) complexes with thiophenecarboxylic acid, [Cu(3‐TCA)₂(2,2′‐bpy)] ( 1 ), [Cu(3‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 2 ), [Cu(5‐Me‐2‐TCA)₂(H₂O)(2,2′‐bpy)] ( 3 ) and [Cu₂(2,5‐TDCA)(DMF)₂(H₂O)₂(2,2′‐bpy)₂](ClO₄)₂ ( 4 ) (where 3‐TCA = 3‐thiophenecarboxylic acid; 3‐Me‐2‐TCA = 3‐methyl‐2‐thiophenecarboxylic acid; 5‐Me‐2‐TCA = 5‐methyl‐2‐thiophenecarboxylic acid; 2,5‐TDCA = thiophene‐2,5‐dicarboxylic acid; 2,2′‐bpy = 2,2′‐bipyridyl; DMF = N,N‐dimethylformamide), were synthesized. Compounds 1 – 4 were extensively characterized using both analytical and spectroscopic methods. Additionally, the solid‐state structures of 1 and 4 were unambiguously established from single‐crystal X‐ray diffraction studies. The hexacoordinated Cu(II) centre in 1 (CuO₄N₂) is a distorted octahedral geometry whereas the pentacoodinated 4 (CuO₃N₂) has distorted square pyramidal geometry. Compounds 1 and 4 exhibit intermolecular hydrogen bonding which leads to the formation of two‐ and three‐dimensional supramolecular architectures, respectively. Spectrophotometric and computational investigations suggest that these compounds bind with DNA in minor groove binding such that K_b = 4.9 × 10⁵ M^?1 and K_sv = 3.4 × 10⁵ M^?1, and binding score of ?5.26 kcal mol^?1. The binding affinity of these complexes to calf thymus DNA is in the order 2 > 3 > 4 > 1 . Methyl‐substituted thiophene ring increases the DNA binding affinity whereas unsubstituted thiophene ring DNA binding rate is reduced. The methyl group on the thiophene ring would sterically hinder π–π stacking of the ring with DNA base pairs, and subsequently they are involved in hydrophobic interaction with the DNA surface rather than partial intercalative interaction. Compounds 1 – 4 show pronounced activity against B16 mouse melanoma skin cancer cell lines as measured by MTT assay yielding IC₅₀ values in the micromolar concentration range. The compounds could prove to be efficient anti‐cancer agents, since at a concentration as low as 2.1 μg ml^?1 they exerted a significant cytotoxic effect in cancer cells whereas cell viability was not affected in normal cells.     

Electrochemical,magnetic, catalytic and DNA cleavage studies of binuclear copper(II) complexes derived from pendant substituted tetraaza macrobicyclic compartmental ligands

A series of macrobicyclic unsymmetrical binuclear copper(II) complexes of compartmental ligands were synthesized from the Schiff base condensation of 1,8[N,N′-bis{(3-formyl-2-hydroxy-5-methyl)benzyl}]-1,4,8,11- tetraaza-5,5,7,12,12,14-hexa methylcyclotetradecane with diamines like 1,2-diamino ethane, 1,3-diamino propane, 1,4-diaminobutane, 1,2-diaminobenzene and 1,8-diaminonaphthalene. The complexes were characterized by elemental and spectral analysis. Electrochemical studies of the copper(II) complexes show two irreversible one-electron reduction processes around E¹_pc = −0.70 to −1.10 V and E²_pc = −0.98 to −1.36 V. ESR spectra of the binuclear copper(II) complexes show a broad signal at g = 2.10 and μ_eff values in the range 1.46–1.59 BM, which convey the presence of antiferromagnetic coupling. Cryomagnetic investigation of the binuclear complexes [Cu₂L³(ClO₄)](ClO₄) and [Cu₂L⁴(ClO₄)](ClO₄) show that the observed −2J values are 144 and 216 cm⁻¹, respectively. The observed initial rate (V_in) for the catalytic hydrolysis of p-nitrophenyl phosphate by the binuclear copper(II) complexes were in the range 1.8 × 10⁻⁵ to 2.1 × 10⁻⁵ Ms⁻¹. The initial rate (V_in) for the catalytic oxidation of catechol to o-quinone by the binuclear copper(II) complexes were in the range 2.7 × 10⁻⁵ to 3.5 × 10⁻⁵ Ms⁻¹. The copper(II) complexes have been found to promote cleavage of plasmid pBR 322 DNA from the supercoiled form I to the open circular form II.     

Synthesis,characterization, DNA interaction and cleavage activity of new mixed ligand copper(II) complexes with heterocyclic bases

Mixed ligand complexes having the formulae Cu(RPO)₂Py₂, Cu(RPO)₂Im₂ and Cu(DBO)₂Py₂ [RPO = resacetophenone oxime, DBO = 2,4-dihydroxybenzophenone oxime, Py = pyridine and Im = imidazole] have been synthesized and characterized by UV–Vis, IR, ESR, cyclic voltammetry and magnetic susceptibility methods. Absorption studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of 10⁴–10⁵ M⁻¹. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of the adducts was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes cleaved supercoiled DNA by hydrolytic and oxidative paths. The oxidative path dominates the hydrolytic cleavage. The hydrolytic cleavage of DNA is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO or the singlet oxygen quencher azide ion.     

Binding interactions of mixed ligand copper(II) amino acid Schiff base complexes with biological targets: Spectroscopic evaluation and molecular docking

Three mixed ligand copper(II) complexes [Cu(o ‐vanillin‐l ‐tryptophan Schiff base)(diimine)] (diimine =2,2′‐bipyridine ( 1 ), 1,10‐phenanthroline ( 2 ) and 5,6‐dimethyl‐1,10‐phenanthroline( 3 )) were synthesized and characterized using analytical and spectral methods. The molecular structures of 1 – 3 were optimized using density functional theory (DFT) at B3LYP/LanL2DZ levels in the gas phase. Spectral and DFT studies suggest a distorted square pyramidal geometry around the copper ion. Binding interactions of 1 – 3 with calf thymus DNA and bovine serum albumin protein were studied using UV–visible and fluorescence spectroscopies, viscometric titrations and cyclic voltammetry and also using molecular docking analysis. Studies of the binding of the complexes with calf thymus DNA reveal intercalation, which is supported by molecular docking simulation. The DNA cleavage nature of 1 – 3 with pUC19 DNA shows that the complexes can cleave DNA without any external agents, and the efficiency follows the order 1  >  3  >  2 . Synchronous and three‐dimensional fluorescence spectral studies suggest that the secondary structures of the protein are altered by the complexes. Antioxidant studies reveal that the complexes have significant radical scavenging activity against DPPH. In vitro cytotoxic activity of the complexes was evaluated against breast cancer cells (MCF‐7), revealing that complex 2 exhibits higher cytotoxicity than the other complexes. Nuclear chromatin condensation and fragmentation were observed with DAPI staining assay. The mitochondrial membrane potential damage was studied by FITC staining assay. Flow cytometric analysis suggests that all the metal complexes induce cell apoptosis.     

DNA binding,cleavage, and cytotoxicity of binuclear phenolate nickel(II) complexes

Three binuclear phenolate complexes, [Ni₂(L¹)₂(OAc)](BPh₄)·DMF (1), [Ni₂(L²)₂(OAc)](BPh₄) (2), and [Ni₂(L³)₂(OAc)](OH)·3H₂O (3), where L¹ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methyl-phenol, L² = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methoxy-phenol, and L³ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-tert-butyl-phenol), have been synthesized. Single-crystal diffraction reveals that all the metal atoms are in a distorted octahedral geometry. The interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by UV–vis absorption, fluorescence emission, and circular dichroism spectroscopy and viscosity measurements. Furthermore, DNA cleavage mechanism shows that the complexes may be capable to promote DNA cleavage through oxidative DNA damage pathway, which is indicative of the involvement of hydroxyl radical, singlet oxygen, or singlet oxygen-like entity in the cleavage process. Cytotoxicity studies on the Hela and MCF-7 cancer cell lines show that complexes 1–3 exhibit excellent activity toward the tested tumor cell lines with respect to the standard drug carboplatin, revealing that they have the potential to act as effective metal-based anticancer drugs.     

Organoruthenium (II) complexes featuring pyrazole‐linked Schiff base ligands: Crystal structure,DNA/BSA interactions,cytotoxicity and molecular docking

Half‐sandwiched ruthenium (II) arene complexes with piano stool‐like geometry with the general formula [(p‐cymene)RuClL¹] and [(p‐cymene)RuClL²] [where L¹ = (Z)‐N′‐((1,3‐diphenyl‐1H‐pyrazol‐4‐yl)methylene)furan‐2‐carbohydrazide and L² = (Z)‐N′‐((1,3‐diphenyl‐1H‐pyrazol‐4‐yl)methylene)thiophene‐2‐carbohydrazide] were synthesized and characterized. The single crystal X‐ray data revealed that the complexes belong to the same crystal system (monoclinic) with octahedral geometry, where the ruthenium atom is surrounded by hydrazone ligand coordinated through ON atoms, one chloride labile co‐ligand and the remaining three coordination sites covered by an electron cloud of p‐cymene moiety. The interaction between the complexes and DNA/bovine serum albumin (BSA) was evaluated using absorption and emission titration methods showing intercalative modes of interaction. The DNA cleavage ability of the complexes was checked by agarose gel electrophoresis method exhibiting the destruction of DNA duplex arrangement. To understand the interaction between ruthenium complex and DNA/BSA molecule, molecular docking studies were performed. In vitro cytotoxicity of the complexes was examined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay on human lung cancer cell line, A549, and found that at lower IC₅₀, cell growth inhibition has occurred. Similarly, the IC₅₀ values of the complexes treated with cancerous cell lines have produced a significant amount of lactase dehydrogenase and nitrite content in the culture medium, which were evaluated as apoptosis‐inducing factors, suggesting that the ruthenium (II) arene hydrazone complexes with pyrazole ligands have promising anticancer activities.     

Synthesis,characterization, DNA interaction,apoptosis and molecular docking of Cu(II) and Mn(II) complexes with endo‐norbornene‐cis‐5,6‐dicarboxylic acid

Two new novel complexes, [Cu₄(Endc)₄(phen)₄]⋅7(H₂O)⋅2(O) and [Mn₂(Endc)₂(phen)₂(H₂O)₂]⋅(H₂O) (phen =1,10‐phenanthroline, H₂Endc = endo ‐norbornene‐cis ‐5,6‐dicarboxylic acid), were synthesized and structurally characterized using IR and ¹H NMR spectroscopies, elemental analysis and single‐crystal X‐ray diffractometry. Their reactivity with calf thymus DNA and HeLa cell DNA was measured using UV absorption and fluorescence spectroscopies. The results indicated that these complexes can bind to DNA with different binding affinity. Gel electrophoresis assay demonstrated the ability of the complexes to cleave pBR322 plasmid DNA. Apoptotic study showed that the complexes exhibit significant cancer cell inhibitory rates. Eventually, the complexes can suitably dock with a special DNA (PDB ID: 1AIO).