Water‐soluble Schiff base Cu(II) and Zn(II) complexes: Synthesis,DNA targeting ability and chemotherapeutic potential of Cu(II) complex for hepatocellular carcinoma – in vitro and in vivo approach

Reliable compounds with low toxicity are tempting potential chemotherapeutics. With an aim of achieving less toxic but more potent metallodrugs, four new‐generation hydrophilic Cu(II) and Zn(II) complexes with DNA‐targeting properties were synthesized and characterized using various physicochemical data. The excellent DNA binding and cleavage results confirmed the mode of binding of DNA with the complexes and their ability to denature it. The profound in vitro cytotoxicity exhibited by complex 3 against a panel of cell lines (HeLa, MCF‐7 and HepG‐2) along with NHDF (normal human dermal fibroblasts) with distinct activity towards HepG‐2 and low toxicity to NHDF prompted in vivo studies of induced hepatocellular carcinoma‐affected Swiss albino rats. On evaluating various serum hepatic, biological and histopathological parameters, complex 3 showed excellent activity in restoring the damaged liver to normal. As a means of identifying the pathway of DNA damage, flow cytometric evaluation of cell cycle analysis was performed, which revealed S phase arrest‐induced apoptosis in HepG‐2 cells by complex 3 , making it a cell cycle‐specific drug.     

Heteroleptic Schiff base complexes containing terpyridine as chemical nucleases and their biological potential: A study of DNA binding and cleaving,antimicrobial and cytotoxic tendencies

Amidst the very many metallodrugs for the treatment of cancer regularly reported, the development of the next generation of compounds with an aim of overcoming the shortcomings by enhancing biological activity and cytotoxicity but exhibiting low toxicity is essential. Herein we report such octahedral metal(II) complexes ( 1 – 12 ) containing triazole‐derived Schiff base as the scaffold. The complexes were synthesized and characterized by means of elemental analysis and various spectroscopic techniques. The complexes were subjected to various investigations that involved their interaction with calf thymus DNA and supercoiled pBR322 DNA. In vitro antimicrobial studies were also conducted in addition to the use of spectrophotometric, spectrofluorometric, cyclic voltammetric and hydrodynamic techniques. Although all complexes showed activity, complex 9 revealed excellent DNA proclivity, DNA cleaving tendencies and antimicrobial efficacy. All copper(II) complexes were evaluated for their antiproliferative activity against a panel of human cancer cell lines (HeLa, Hep‐2, MCF‐7 and NHDF). Complexes 1 – 12 showed activity against all the cell lines with low toxicity towards normal cell line, and the activity of complex 9 towards Hep‐2 was prominent. The effect of the ligand system on the complexes is also discussed along with the importance of tuning the ligand system.     

Role of Knoevenagel condensate pyrazolone derivative Schiff base ligated transition metal complexes in biological assay and cytotoxic efficacy

A new bioessential Knoevenagel condensate Schiff base ligand (L) was synthesized by the reaction of 3‐(4‐hydroxy‐3‐methoxybenzyl)pentane‐2,4‐dione and 4‐aminoantipyrine. The ligand forms monomeric divalent transition metal complexes ( 1 – 4 ) which were characterized using spectral and analytical data. All these complexes have the general formula [ML]Cl₂, where M = Co(II), Ni(II), Cu(II) and Zn(II). They are electrolytic in nature and adopt square planar geometry. The binding propensity of these complexes with calf thymus DNA was investigated using absorption spectrophotometric titration, cyclic voltammetry and viscosity measurements. The binding constant values imply that the complexes bind with DNA via intercalation mode. The in vitro antibacterial and antifungal activities reveal that the complexes have good antimicrobial efficacy against a set of pathogens. The nucleolytic cleavage activity of these complexes on pUC18 DNA was investigated using agarose gel electrophoresis. Also, the in vitro cytotoxicity of the synthesized complexes against a panel of human tumour cell lines (MCF‐7 and HeLa) and normal cell lines (NHDF and HEK) was assayed using the MTT method. Interestingly, complex 1 exhibits more potent anticancer activity than cisplatin and other complexes.     

Theoretical,antimicrobial, antioxidant,in vitro cytotoxicity,and cyclin-dependent kinase 2 inhibitor studies of metal(II) complexes with bis(imidazol-1-yl)methane-based heteroscorpionate ligands

Abstract

A series of C-centered heteroscorpionate-based homoleptic manganese(II), nickel(II), and copper(II) complexes of type [M(L^1–3)₂] (1–9) have been synthesized by using the 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). The geometric parameters of the complexes were determined using UV-vis and theoretical studies suggesting distorted octahedral geometry around metal(II) ion. Frontier molecular orbital analysis supports bioefficacy of the complexes. Antimicrobial activity of the metal(II) complexes were determined against two Gram(–ve) (Escherichia coli and Klebsiella pneumoniae) and two Gram(+ve) (Bacillus cereus and Staphylococcus aureus) bacteria, and three fungal (Candida albicans, Candida glabrata, and Candida krusei) strains. Antioxidant activity of nickel(II) and copper(II) complexes were evaluated against ABTS, DPPH, and H₂O₂ free radicals. In vitro cytotoxicity activity of nickel(II) and copper(II) complexes against human breast adenocarcinoma (MCF-7), cervical (HeLa), and lung (A549) cancer cell lines along with one normal human dermal fibroblasts (NHDF) cell line were carried out by MTT assay, which shows the potent activity of copper(II) complex 8 with respect to the standard drug cisplatin. Molecular docking studies evidence the interaction of complexes with cyclin-dependent kinase 2 receptor (CDK2).     

Transition metal complexes of 6‐mercaptopurine: Characterization,Theoretical calculation,DNA‐Binding,molecular docking,and anticancer activity

6‐mercaptopurine (6‐MP) is used for treating various cancers and autoimmune disorders. A few examples of transition metal complexes of 6‐MP have been shown to enhance its anticancer activity, but many remain untested. We isolated five highly stable and colored metal complexes of 6‐MP and confirmed their structures by elemental analysis, spectral, and thermal techniques. Infrared (IR) spectra revealed that 6‐MP is a bidentate ligand that interacts through sulfur and pyrimidine nitrogen in a 1:2 (M:L) molar ratio. The magnetic susceptibility and electron paramagnetic resonance (EPR) spectra for the Cu(II) complex revealed an octahedral arrangement around the metal ion with strong covalent bonding. The fully optimized geometries of the metal structures obtained using density function theory (DFT)/B3LYP calculations were used to verify the structural and biological features. DNA titration revealed that the octahedral Cu(II) complex has a critical binding constant value of K_b = 8 × 105. Docking studies using three different cancer protein receptors were used to predict the biological applications of the synthesized drug‐metal complexes. Finally, cytotoxicity assays against a myeloma cancer cell line (MM) and a colon cancer cell line (Caco‐2) revealed favorable anticancer activity for the copper complex, exceeding that of the gold‐standard chemotherapeutic cisplatin.     

Applying Cu(II) complexes assisted by water-soluble porphyrin to DNA binding and selective anticancer activities

Cancer is one of the killers endangering human health and its treatment has always been a focus of the medical community. For anticancer drugs, water-soluble porphyrin and Schiff bases have always been of interest. We report here three Cu(II)-based complexes functionalized by water-soluble cationic porphyrin and hydrazine Schiff base, which were prepared and evaluated for their biological activity. The three Cu(II) complexes all exhibited potent binding affinity to calf thymus DNA, the strongest interaction being between CuP2 and DNA. We studied the cytotoxicity of the complexes and ligands against different types of cancer cells (A549, H-1975, HepG2 and T47D), results showing the ligands are less cytotoxic; therefore, the anticancer activity of the complexes is improved by complexation. Furthermore, the cytotoxicity of ligands and complexes was also evaluated against the normal cell line Hs 578Bst, complexes showing more negligible cytotoxicity than ligand. Moreover, the cellular uptake of these Cu(II) complexes was investigated using the extraction method and results suggested that CuP2 exhibits the best cellular uptake towards H-1975 cells. Interestingly, fluorescence microscopy experiments and flow cytometric analysis (cell cycle) were used to further investigate the potent anticancer activities.     

Biomolecular docking,antimicrobial and cytotoxic studies on new bidentate schiff base ligand derived metal (II) complexes

Three new metal complexes [Cu(L)₂] (1), [Co(L)₂] (2) and [Zn(L)₂] (3) have been prepared by the reaction of hydrated salts of metal (II) acetate with new Schiff base ligand HL, [2‐((4‐(dimethylamino)phenylimino)methyl)‐4,6‐di‐t‐butylphenol] and characterized by different physico‐chemical analyses such as elemental analysis, single XRD, ¹H NMR, FTIR and UV–Vis spectroscopic techniques. Their biomolecular docking, antimicrobial and cytotoxicity studies have also been demonstrated. The proposed structure of Schiff base ligand HL and complex 2 are confirmed by Single crystal X‐ray crystallography study. This analysis revealed that metal (II) complexes remain in distorted tetrahedral coordination environments. The electronic properties such as HOMO and LUMO energies are carried out by gaseous phase DFT/B3LYP calculations using Gaussian 09 program. Complex 1 showed a good binding propensity to the DNA and HSA, during the assessment of docking studies. Schiff base ligand HL and its metal (II) complexes, 1–3 screened for their in vitro antimicrobial activities using the disc diffusion method against selected microbes. Complex 1 shows higher antimicrobial activity than complexes 2, 3 and Schiff base ligand HL. According to the results obtained from the cytotoxic studies, Schiff base ligand HL and its metal (II) complexes 1–3 have better cytotoxicity against MCF‐7 cell lines with potency higher than the currently used chemotherapeutic agent cyclophosphamide.     

Novel Cr (III), Fe (III) and Ru (III) Vanillin Based Metallo‐Pharmaceuticals for Cancer and Inflammation Treatment: Experimental and Theoretical Studies

In this study, three novel complexes comprising trivalent Cr (III), Fe (III) and Ru (III) with imine ligand derived from 2‐amino‐3‐hydroxypyridine and o‐vanillin (H₂L) have been synthesized and characterized via wide range of spectroscopic and analytical tools such as ¹H NMR and ¹³C NMR, infrared (IR) and UV–Vis spectrophotometry, conductivity and magnetic measurements. The obtained results along with DFT data confirmed a 1:1 (metal: ligand) stoichiometry with non‐planner geometries for the three complexes. The binding action and the docking study of the prepared metal‐complexes to calf thymus DNA was also studied by absorption spectra and viscosity technique, which revealed that the three complexes interact strongly with DNA through intercalative binding mode. Significantly, these metal‐imine complexes showed strong and efficient anti‐inflammatory and antimicrobial activities against various gram‐positive (Microccus luteus), gram‐negative (Escherichia coli and Serratia marcescence) bacteria, and three strains of fungus. Moreover, all complexes exhibited more potent cytotoxicity effect on the outgrowth of different types of carcinoma cells, including human colon (HCT‐116 cell line), breast (MCF‐7 cell line), and hepatic cellular (HepG‐2), than the clinically‐proven Vinblastine standard.     

DNA fastening and scission actions of Cu(II), Co(II), Ni(II) and Zn(II) complexes: synthesis,spectral characterization and cytotoxic study

A heterocyclic compound, 2‐(aminomethyl)benzimidazole dihydrohydrochloride, was treated with nitrobenzaldehyde to form a Schiff base that was made to react with divalent metals. A co‐ligand, either 1,10‐phenanthroline or 2,2′‐bipyridine, was added to this mixture to obtain metal chelators of type [ML(co‐L)₂]Cl₂. They were in 1:1:2 stoichiometry ratio, which was characterized by various spectroscopic techniques that suggested an octahedral geometry around the central metal ions. These complexes were investigated for their binding affinities with calf thymus (CT) DNA, using various techniques, such as UV–Vis, viscosity, cyclic voltammetry (CV), etc. The binding interaction studies revealed intercalation as the possible binding mode of the complexes with the CT DNA. In addition, these complexes were screened for their antimicrobial potential and DNA denaturing tendencies using gel electrophoretic assay. The antimicrobial screening investigation showed that the complexes behaved as better antimicrobial agents than the ligand, especially, complex 5 shows exceptional activity even in the electrophoretic assay along with the antimicrobial efficacy. Moreover, complex 5 was able to denature the plasmid DNA better than the other compounds. All the compounds were screened for cytotoxic efficacy, and the IC₅₀ values suggest that the compounds possess cytotoxic activity to some extent that is almost the same as the activity of cisplatin.     

Biocatalysis,DNA–protein interactions,cytotoxicity and molecular docking of Cu(II), Ni(II), Zn(II) and V(IV) Schiff base complexes

Four mononuclear metal complexes (Cu(II) ( 1 ), Ni(II) ( 2 ), Zn(II) ( 3 ) and V(IV) ( 4 )) were synthesized using the Schiff base ligand 2,2′‐{cyclohexane‐1,2‐diylbis[nitrilo(1E )eth‐1‐yl‐1‐ylidine]}bis[5‐(prop‐2‐yn‐1‐yloxy)phenol] and structurally characterized by various spectral techniques. The catecholase‐mimicking activities of 1 – 4 were investigated and the results reveal that all the complexes have ability to oxidize 3,5‐di‐tert ‐butylcatechol (3,5‐DTBC) to 3,5‐di‐tert ‐butylquinone in aerobic conditions. Electrospray ionization mass spectrometry studies were performed for 1 – 4 in the presence of 3,5‐DTBC to determine the possible complex–substrate intermediates. X‐band electron paramagnetic resonance spectroscopy results indicate that the metal centres are involved in the catecholase activity. Ligand‐centred radical generation was further confirmed by density functional theory calculation. The phosphatase‐like activity of 1 – 4 was investigated using 4‐nitrophenylphosphate as a model substrate. All the complexes exhibit excellent phosphatase activity in acetonitrile medium. The interactions of 1 – 4 with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA) protein were investigated using absorption and fluorescence titration methods. All the complexes strongly interact with CT‐DNA and BSA protein. The complexes exhibit significant hydrolytic cleavage of supercoiled pUC19 DNA. Complexes 1 – 4 exhibit significant in vitro cytotoxicity against MCF7 (human breast cancer) and MIA‐PA‐CA‐2 (human pancreatic cancer) cell lines. Moreover, the molecular docking technique was employed to determine the binding affinity with DNA and protein molecules.     

Theoretical Investigation by DFT and Molecular Docking of Synthesized Oxidovanadium(IV)-Based Imidazole Drug Complexes as Promising Anticancer Agents

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (K_b) value for the [VO(SO₄)(MNZ)₂] H₂O complex was promising, which was 2.0 × 10⁶ M⁻¹. Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents.     

Synthesis,cytotoxicity, apoptosis and molecular docking studies of novel phenylbutyrate derivatives as potential anticancer agents

Phenylbutyrate (PB), a small aromatic fatty acid, has been known as an interesting compound with the ability of anti-proliferation and cell growth inhibition in cancer cells. In the present study, a series of PB derivatives were synthesized by Passerini multicomponent reaction and their cytotoxic activities against various human cancer cell lines including A549 (non-small cell lung cancer), MDA-MB-231 (breast cancer), and SW1116 (colon cancer) were evaluated. The results revealed that B9, displayed significantly higher in vitro cytotoxicity with IC₅₀ of 6.65, 8.44 and 24.71 μM, against A549, MDA-MB-231 and, SW1116, respectively, in comparison to PB. The effects of these compounds on the proliferation of MCF-10A as non-tumoral breast cell line, showed good selectivity of the compounds between tumorigenic and non-tumorigenic cell lines. Moreover, B9 has indicated apoptosis-inducing activities to MDA-MB-231 cancer cell line in a dose-dependent manner. The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to predict the binding sites and binding orientation of the compounds to these targets.     

Synthesis,characterization, DNA binding and cleavage activity of homoleptic zinc(II) β-oxodithioester chelate complexes

New homoleptic zinc(II) complexes, [Zn(L)₂], where L = methyl-3-hydroxy-(3-pyridyl)-2-propenedithioate L1 1, and methyl-3-hydroxy-(4-pyridyl)-2-propenedithioate L2 2, have been synthesized and characterized by elemental (C, H, and N) analysis, ESI-MS, and (IR, UV–vis, NMR) spectroscopy; the structure of 1 has been deduced by X-ray crystallography. The DNA binding and cleavage activity of the complexes have been studied. The cleavage potential of pBR322 DNA by 1 and 2 has been checked. Complex 1, which contains nitrogen of the pyridine group in the 3-position enhances DNA cleavage potential in the presence of ascorbic acid; however, the complex is protective against DNA cleavage in the presence of DMSO or H₂O₂. Also, 1 causes cytotoxicity against the MCF-7 breast cancer cell line. The efficient cytotoxic activity and DNA cleavage ability of 1 in the presence of ascorbic acid shows its potential anticancer properties and the need for further investigations of its potential as an anticancer drug.     

Synthesis,cytotoxicity, topoisomerase I inhibition and molecular docking of novel phosphoramide mustard sophoridinic acid analogues

A series of novel phosphoramide mustard sophoridinic acid analogues, consisting of nitrogen mustard group and sophoridinic acid scaffold, have been designed, synthesized and evaluated for their topoisomerase inhibitory activity as well as cytotoxicity against six tumor cell lines (SMMC‐7721, LoVo, MCF‐7, K562, S180 and H22) and a normal cell line (L929). Among the compounds tested, five were found to be potent inhibitors and exhibited potent cytotoxicity against S180 and H22 cell lines with IC₅₀ values of 1–4 μM. Further mechanistic studies showed that this class of compounds acted as novel topoisomerase I (Topo I) catalytic inhibitors by preventing the binding of Topo I to DNA and inhibiting the cleavage of DNA, and molecular docking studies revealed that the binding energy for these compounds was comparable to that for classic Topo I inhibitors CPT and HCPT, indicating that the compounds have an interaction with DNA and Topo I.     

Synthesis and cytotoxicity study of gold(III) porphyrin complexes and their derivative in breast cancer cells

Gold(III) [Au(III)] complexes exhibit potential anticancer activities. A series of Au(III) porphyrin complexes containing different meso-substituent groups (phenyl, methoxyphenyl, butyloxyphenyl, octyloxyphenyl, and decyloxyphenyl) was synthesized. The synthesized compounds were characterized using mass spectrometry, infrared spectroscopy, UV–visible and fluorescence spectroscopy, and electron paramagnetic resonance spectroscopy. Moreover, the in vitro cytotoxicity of these Au(III) porphyrin complexes was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide surrogate viability assay on an MCF7 human breast cancer cell line. The Au(III) complexes with 5,10,15,20-tetraphenylporphyrin (AuTPP) and 5,10,15,20-tetrakis(4-methyloxyphenyl)porphyrin (AuTOMPP) demonstrated high anticancer activity with IC₅₀ values against MCF7 cells at 4.30 and 25.35 µM, respectively. The toxicity of the Au(III) porphyrin complexes against the LLC-MK2 rhesus monkey kidney epithelial cell line, a representative normal cell line, was investigated. All the tested Au(III) porphyrin complexes were non-cytotoxic in LLC-MK2 cells. For AuTPP, more than 80% LLC-MK2 cell viability was observed at concentrations lower than 5 μM.     

Two MnII,CuII complexes derived from 3,5‐bis(1‐imidazoly) pyridine: Synthesis,DNA binding,Molecular docking and cytotoxicity studies

Two complexes [MnL₂ (H₂O)₂]·2ClO₄ (complex 1) and [CuL(H₂O)₃]·2NO₃ (complex 2) (where L = 3,5‐bis(1‐imidazoly) pyridine) were designed and synthesized. The structures of the complexes were characterized by X‐ray crystallography, elemental analyses, and infrared spectrum. The interaction capacity of the complexes with calf thymus DNA has been investigated by UV and fluorescence spectroscopy. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. Efficient binding properties of DNA were established by UV–vis, fluorescence, and gel electrophoresis. The intrinsic binding constants (K_b) were calculated to be 0.1524, 0.1041 for complexes 1–2, respectively. The cytotoxic activity of the two complexes exhibited a higher cytotoxicity against HeLa cell lines and lower cytotoxicity toward the normal cell lines. Flow cytometry demonstrated the cancer cell inhibitory rate of two complexes. Furthermore, computer‐aided molecular docking studies were performed to visualize the binding mode of the drug candidate at the molecular level. Interestingly, complex 1 exhibited a significant cancer cell inhibitory rate than cisplatin and other complexes.     

Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes

Three silver(I) dipeptide complexes [Ag(GlyGly)]_n(NO₃)_n (AgGlyGly), [Ag₂(GlyAla)(NO₃)₂]_n (AgGlyAla) and [Ag₂(HGlyAsp)(NO₃)]_n (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 μM.     

Preparation,Structural characterization and DNA binding/cleavage affinity of new bioactive nano‐sized metal (II/IV) complexes with oxazon‐Schiff's base ligand

A novel oxazon‐Schiff's base ligand named (E)‐3‐(2‐(4‐(diethylamino)‐2‐hydroxybenzylidene)hydrazineyl)‐2H‐benzo[b][1,4]oxazin‐2‐one (HL) has been synthesized in addition to its nano‐sized divalent and tetravalent Mn (II), Co (II), Ni (II), Cu (II), Zn (II) and Pt (IV) complexes. The structures and geometries of the synthesized compounds have been confirmed using the different analytical and spectroscopic tools such as elemental analysis, uv–vis., IR, HR‐MS, ¹H NMR, ESR, TGA, XRD, EDX, TEM, SEM, AFM, magnetic and molar conductivity measurements. The elemental analyses confirm 1 M: 2 L stoichiometry of the type [PtL₂].2Cl and [ML₂] (M = Mn (II), Co (II), Ni (II), Cu (II) and Zn (II)). The FT‐IR spectral studies illustrated that the ligand bind to the metal ions through the phenolic hydroxy oxygen, azo methine nitrogen carbonyl oxazin oxygen. The spectral tools; UV–Vis, ligand field parameters and ESR in addition to the magnetic moment measurements confirmed octahedral geometry around the metal centres. The absence of coordinated or hydrated water complexes were confirmed by thermal analysis data of the complexes. The electron transfer reactions for the complexes have been studied by cyclic voltammetry. XRD, SEM, TEM, and AFM images confirmed nano‐sized particles and homogeneous distribution over the complex surface. The mode of binding of the complexes with DNA has been performed through electronic absorption titration and viscosity studies. The reaction between the metal complexes and DNA were studied by DNA cleavage. In general, MCF‐7 cell were least sensitive to the tested compounds and all compounds were considerably more toxic to the studied cancer cell lines than to the normal cell line HepG‐2. The binding mode of the compounds and DNA was preferably via intercalation. In addition, these results were confirmed based on theoretical studies . Finally, a linear and exponential correlation between interaction constant (K_b) and IC₅₀ for two human cancer cell was observed.     

Synthesis,spectral characterization,antioxidant, anticancer in vitro,and DNA cleavage studies of a series of ruthenium(II) complexes bearing Schiff base ligands

Ruthenium(II) complexes with 2-acetylpyridine-thiosemicarbazones (L¹–L⁴) were synthesized and characterized by analytical and spectral (FT-IR, UV–vis, NMR [¹H, ¹³C and ³¹P], and ESI-Mass) methods. Systematic biological investigations, free radical scavenging, anticancer activities, and DNA cleavage studies, were carried out for the complexes. Antioxidant studies showed that the complexes have significant antioxidant activity against DPPH, hydroxyl, nitric oxide radicals and hydrogen peroxide assay. The in vitro cytotoxicity of complexes against breast cancer (MCF-7) cell line was assayed showing high cytotoxicity with low IC₅₀ values indicating their efficiency in destroying the cancer cells even at very low concentrations. The DNA cleavage studies showed that the complexes efficiently cleaved DNA.     

Spectroscopic Study of DNA Hydrolysis,DNA Intercalative,and Electrostatic Interaction Activity Exerted by Drug Based Coordination Compounds

Our work emphasized on synthesizing and characterizing neutral mononuclear copper(II) complexes with second generation fluoroquinolone drug ciprofloxacin (CFL) and some bipyridine derivatives (Aⁿ) of type [Cu(CFL)(Aⁿ)Cl] · 2H₂O. The DNA binding free energies were evaluated by studying the effect of salt concentrations on DNA binding. DNA interactions were investigated by using DNA melting temperature studies, viscosity measurements, absorption titration, and gel electrophoresis experiments. Also superoxide dismutase (SOD)‐like activity (IC₅₀ values) and antibacterial activity of metal complexes were studied. To validate the proper mechanistic pathway for plasmid DNA cleavage, gel electrophoresis experiments were carried out in presence of radical scavenging agents. The bactericidal activity of metal complexes was evaluated in terms of colony forming unit.