Synthesis,cytotoxicity and DNA-binding properties of Pd(II), Cu(II) and Zn(II) complexes with 4′-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2′:6′,2″-terpyridine

Pd(II), Cu(II) and Zn(II) complexes (1–3) based on 4′-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2′:6′,2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, K562 and MCF-7 cell lines in vitro was measured by MTT method. The DNA binding property of the complexes was evaluated by UV, fluorescence, CD spectroscopies and thermal denaturation. The cytotoxicity of complexes 1 and 3 against all the tested cell lines is better than that of cisplatin. Complexes 1 and 2 exhibit 7- and 4-folds higher cytotoxicity than cisplatin against Bel-7402 cell line. Complex 3 displays the highest cytotoxicity against all the cell lines tested, and shows 7-, 14-, 8-, 11- and 8-folds higher cytotoxicity than cisplatin against Bel-7402, A549, Hela, K562 and MCF-7 cell lines. The complexes bind to DNA via intercalation mode and complex 3 stabilizes the G-quadruplex. The results reveal that all the complexes display high cytotoxicity against all the tested cancer cell lines, and complex 3 is selective for G-quadruplex over duplex DNA.     

Platinum(II) Complexes with 1,10‐Phenanthroline and Hydrophilic Alkoxyacetate Ligands as Potential Antitumor Agents

Four platinum complexes, formulated as [Pt(phen)(OCOCH₂OR)₂] (phen=1,10‐phenanthroline, R=Me, Et, ⁱPr, or ^tBu), have been synthesized and well characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR and ESI‐MS spectroscopy. Replacing chloride groups of the precursor Pt(phen)Cl₂ with alkoxyacetate anions greatly improved the aqueous solubility and cytotoxicity of the resulting platinum complexes. The in vitro cytotoxicity study revealed that complexes 1 – 3 were active in vitro towards four human tumor cell lines, especially complex 1 which exhibited prominent in vitro cytotoxic activity against HCT‐116 cell lines comparable to cisplatin and oxaliplatin. Flow cytometry assay indicated that representative complexes 1 and 2 exerted cytotoxicity on HCT‐116 cell lines through inducing cell apoptosis and blocking cell cycle progression in the S or G2/M phases. The interaction of representative complexes with pET28a plasmid DNA was tested by agarose gel electrophoresis, which demonstrated that complexes 1 and 2 were capable of distorting plasmid DNA mainly by covalent binding and degradation effect.     

Novel Oxaliplatin Derivatives with 1‐(Substituted Benzyl)azetidine‐3,3‐dicarboxylate Anions. Synthesis,Cytotoxicity, and Interaction with DNA

A series of oxaliplatin derivatives with (1R,2R)‐N¹‐alkyl‐1,2‐cyclohexane‐1,2‐diamine (alkyl=Bu or ⁱPr) as carrier ligands and 1‐(methoxy‐ or methyl‐substituted benzyl)azetidine‐3,3‐dicarboxylate anions as leaving groups were synthesized and spectrally characterized. Generally, Complexes 10 – 15 with an ⁱPr substituent at N(1) showed higher activities in vitro than carboplatin against MCF‐7 human breast carcinoma and A549 human non‐small‐cell lung cell lines, although they were less potent than oxaliplatin. The typical complex 14 exhibited cytotoxicity superior to that of carboplatin and comparable to that of oxaliplatin against two selected tumor cell lines. Additionally, agarose gel electrophoresis was applied to investigate the DNA‐cleavage ability of complex 14 , which demonstrated that it has a different mode of DNA distortion from that of oxaliplatin.     

Cobalt (II) complex with novel unsymmetrical tetradentate Schiff base (ON) ligand: in vitro cytotoxicity studies of complex,interaction with DNA/protein,molecular docking studies,and antibacterial activity

[C₂₀H₁₇N₃O₂] and cobalt (II) complex [Co(L²)(MeOH)₂].ClO₄, (L² = 4-((E)-1-((2-(((E)-pyridin-2-ylmethylene) amino) phenyl) imino) ethyl) benzene-1, 3-diol) novel Schiff base has been synthesiszed and chracterized by Fourier transform infrared, UV–vis, ¹H-NMR spectroscopy, and elemental analysis techniques. The interaction of Co(II) complex with DNA and BSA was investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroism, and thermal denaturation studies. Our experiments indicate that this complex could strongly bind to CT-DNA via minor groove mechanism. In addition, fluorescence spectrometry of BSA with the complex showed that the fluorescence quenching mechanism of BSA was of static type. The complex exhibited significant in vitro cytotoxicity against three human cancer cell lines (JURKAT, SKOV3, and U87). The molecular docking experiment effectively proved the binding of complex to DNA and BSA. Finally, antibacterial assay over gram-positive and gram-negative pathogenic bacterial strains was studied.     

Three new asymmetric trans-amine(azole)dichloridoplatinum complexes that overcome cisplatin resistance and their reactions with 5′-GMP

Three new asymmetric platinum(II) complexes comprising an isopropylamine ligand trans to an azole ligand were synthesized and fully characterized by ¹H NMR, ¹⁹⁵Pt NMR, IR and elemental analysis. In addition the X-ray crystal structure of all three complexes was determined. The reaction kinetics of the complexes with DNA model base guanosine-5′-monophosphate (GMP) was studied, revealing reaction kinetics comparable to cisplatin. To gain insight in the complexes as potential antitumor agents, cytotoxicity assays were performed on a variety of human tumor cell lines. These assays showed the complexes all to possess cytotoxicity profiles comparable to cisplatin. Furthermore, the complexes largely retain their activity in a human ovarian carcinoma cell line resistant to cisplatin, A2780R, compared to the cisplatin sensitive parent cell line A2780. These results are of fundamental importance, illustrating how platinum complexes of trans geometry can show improved activity compared to cisplatin in both cisplatin sensitive and cisplatin resistant cell lines.     

Synthesis, characterization, and DNA binding of a novel ligand and its Cu(II) complex

A novel naphthalene-2,3-diamine-2-salicylaldehyde (NS) ligand and its mononuclear copper(II) complex (CuNS) have been synthesized and structurally characterized. The UV–vis absorption and emission spectra of NS showed obvious changes on addition of Cu²⁺ solution. The interaction of the compounds with calf thymus DNA and G-quadruplex DNA were investigated by spectroscopic methods and thermal melting assay. The nucleolytic cleavage activity of the compounds was investigated on double-stranded circular pBR322 plasmid DNA and G-quadruplex DNA by electrophoretic mobility shift assay. The results show that CuNS has a greater ability to stabilize G-quadruplex DNA over calf-thymus DNA. The cytotoxicity of the compounds toward HpeG2 cancer cells was also studied, and they showed significant potential for antineoplastic effects.     

Macrocyclic complexes: synthesis,characterization, antitumor and DNA binding studies

Abstract

The present paper deals with the synthesis of novel macrocyclic complexes of the type [MLX]X, where [(M?=?Co(II) (1), and Ni(II) (2) X?=?(Cl₂)]. The complexes are synthesized by the reaction of ligand(L)diquinolineno[1,3,7,9]tetraazacyclododecine-7,15-ethane(14H,16H)-benzene with the corresponding metal salts. The synthesized complexes are thoroughly characterized by elemental analysis, FT-IR, ¹H-NMR, Mass and electronic spectra. The complexes (1) and (2) were evaluated for in vitro cytotoxicity against human breast adenocarcinoma cell (MCF-7). MTT cytotoxicity studies shows both the complexes are most effective. The binding properties of these complexes with calf thymus-DNA were studied by absorption, emission spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum undergoes bathochromic and hypochromic shifts. The absorption spectral results indicate that the intrinsic binding constant (K_b) are 4.8?×?10⁵?M^?1 for (1) and 3.9?×?10⁵?M^?1 for (2) respectively, suggesting that complex (1) binds more strongly to CT-DNA than complex (2). The viscosity measurement results revealed the viscosity of sonicated rod like DNA fragments increased when the complex was added to the solution of CT-DNA. The synthesized ligand and its metal complexes are screened for antibacterial and antifungal activities.     

Synthesis,Characterization, Molecular Modeling,and DNA Interaction Studies of Copper Complex Containing Food Additive Carmoisine Dye

A copper complex of carmoisine dye; [Cu(carmoisine)₂(H₂O)₂]; was synthesized and characterized by using physico-chemical and spectroscopic methods. The binding of this complex with calf thymus (ct) DNA was investigated by circular dichroism, absorption studies, emission spectroscopy, and viscosity measurements. UV-vis results confirmed that the Cu complex interacted with DNA to form a ground-state complex and the observed binding constant (2× 10⁴ M^?1) is more in keeping with the groove bindings with DNA. Furthermore, the viscosity measurement result showed that the addition of complex causes no significant change on DNA viscosity and it indicated that the intercalation mode is ruled out. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the reaction. The results of circular dichroism (CD) suggested that the complex can change the conformation of DNA from B-like form toward A-like conformation. The cytotoxicity studies of the carmoisine dye and its copper complex indicated that both of them had anticancer effects on HT-29 (colon cancer) cell line and they may be new candidates for treatment of the colon cancer.     

Copper(II) Complexes Derived from Schiff Bases Containing 4-Methylbenzylamine as a Core Unit: Cytotoxicity,pBR322-DNA Studies,Biological Assays,and Quantum Chemical Parameters

Bivalent copper complexes, [Cu(SB¹)₂] 1 (SB¹=(2-(4-methylbenzylimino)methyl)-5-methylphenol, [Cu(SB²)₂] 2 (SB²=(2-(4-methylbenzylimino)methyl)-4-bromolphenol), and [Cu(SB³)₂] 3 (SB³=(2-(4-methylbenzylimino)methyl)-4,6-dibromophenol) were synthesized using the Schiff bases prepared from 4-methylbenzylamine (p-tolylmethanamine). These were characterized using a variety of spectro-analytical methods. For all copper complexes, a square planar geometry was determined through spectral analyses. Utilizing molecular orbital energies, the stability of the copper complexes was calculated from quantum chemical characteristics. The kinetic and thermal degradation parameters were calculated from the thermograms. Studies on DNA binding interactions, such as UV absorption and emission, have shown that the manner of DNA binding is intercalative, and the binding constant (K_b) order is 3 > 2 > 1 . Under oxidative and photolytic techniques, the copper complexes outperform the parent Schiff bases in their ability to cleave double-stranded pBR322 DNA. When tested for cytotoxicity on the KB3 and MCF7 cell lines, complexes displayed greater activity than their parent ligands. Studies on the complexes′ in-vitro antibacterial and antioxidant activity showed that they are significantly more powerful than the parent ligands.     

Bifunctional Platinum(II) Complexes with Bisphosphonates Substituted Diamine Derivatives: Synthesis and In vitro Cytotoxicity

A series of N,N′‐dibisphosphonate‐containing 1,3‐propanediamine derivatives ( L1 – L6 ) and their corresponding dichloridoplatinum(II) complexes ( 1 – 6 ) have been synthesized and characterized by elemental analysis, ¹H‐NMR, ¹³C‐NMR, ³¹P‐NMR and HR‐MS spectra. The in vitro antitumor activities of compounds L1 – L6 and 1 – 6 were tested by WST‐8 assay with Cell Counting Kit‐8, indicating that platinum‐based complexes 1 – 6 showed higher cytotoxicity than corresponding ligands L1 – L6 against A549 and MG‐63, especially complex 2 which displayed comparable cytotoxicity to those of cisplatin and zoledronate after 48 h incubation. In addition, complexes 1 – 6 were more active in vitro on osteosarcoma cell line MG‐63 than normal osteoblast cell line hFOB 1.19. The structure‐activity relationship has been summarized based on the in vitro cytotoxicity of three series of platinum complexes from this and our previous studies. The in vitro bone affinity of platinum complexes was also tested by hydroxyapatite (HAP) chromatography in terms of capacity factor K′. Besides, in this paper, representative complex 2 , which has been proved to be a promising antitumor agent with high cytotoxicity and bone HAP binding property, was investigated for its mechanism of action producing cell death against MG‐63.     

Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol side chains

A series of phenanthrene imidazole with polyglycol side chain (2a–2c and 3a–3c) were synthesized and characterized by IR, NMR and MS. The cytotoxicity of 2a–2c and 3a–3c against cancer cell lines (HL-60, BGC-823, Bel-7402 and KB) in vitro were measured using MTT method. The DNA binding properties of 3a–3c were investigated by UV, fluorescence, CD spectroscopies and thermal denaturation. The results indicate that 2a exhibits higher cytotoxicity than cisplatin against BGC-823 and Bel-7402 cell lines, 3b and 3c exhibit higher cytotoxicity than 2b and 2c against BGC-823, Bel-7402 and KB cell lines. The cytotoxic effect of 2a–2c decrease with the increase of side chains length, the cytotoxic effect of 3a–3c increased with the increasing length of side chains against BGC-823, Bel-7402 and KB cell lines. Compounds 3a–3c intercalated DNA with a vertical orientation in the intercalation pocket. The binding constants of 3a–3c with Ct-DNA are 1.68 × 10⁶, 1.51 × 10⁶ and 0.709 × 10⁶ M^?1, respectively. The binding affinity of 3a–3c with Ct-DNA trended to decrease with the increasing length of polyglycol side chains.     

In vitro DNA binding activity and molecular docking reveals pierisin-5 as an anti-proliferative agent against gastric cancer

Abstract

Pierisin-5 is a DNA dependent ADP ribosyltransferase (ADRT) protein from the larvae of Indian cabbage white butterfly, Pieris canidia. Interestingly, Pierisin-5 ADP-ribosylates the DNA as a substrate, but not the protein and subsequently persuades apoptotic cell death in human cancer cells. This has led to the investigation on the DNA binding activity of Pierisin-5 using in vitro and in silico approaches in the present study. However, both the structure and the mechanism of ADP-ribosylation of pierisin-5 are unknown. In silico modeled structure of the N-terminal ADRT catalytic domain interacted with the minor groove of B-DNA for ribosylation with the help of β-NAD⁺ which lead to a structural modification in DNA (DNA adduct). The possible interaction between calf thymus DNA (CT-DNA) and purified pierisin-5 protein was studied through spectral–spatial studies and the blue shift and hyperchromism in the UV–Visible spectra was observed. The DNA adduct property of pierisin-5 protein was validated by in vitro cytotoxic assay on human gastric (AGS) cancer cell lines. Our study is the first report of the mechanism of DNA binding property of pierisin-5 protein which leads to the induction of cytotoxicity and apoptotic cell death against cancer cell lines.

Communicated by Ramaswamy H. Sarma     

Synthesis,structure, and biological active evaluation of a new cyclic tetranuclear copper(II) complex bridged both by oxamido and carboxylate groups

A new tetracopper(II) complex bridged both by oxamido and carboxylato groups, namely [Cu₄(dmaepox)₂(bpy)₂](NO₃)₂·2H₂O, where H₃dmaepox and bpy represent N‐benzoato‐N′‐ (3‐methylaminopropyl)oxamide and 2,2′‐bipyridine, was synthesized, and its structure reveals the presence of a centrosymmetric cyclic tetracopper(II) cation assembled by a pair of cis‐dmaepox^3–‐ bridged dicopper(II) units through the carboxylato groups, in which the endo‐ and exo‐copper(II) ions bridged by the oxamido group have a square‐planar and a square‐pyramidal coordination geometries, respectively. The aromatic packing interactions assemble the complex molecules to a two‐dimensional supramolecular structure. The reactivity toward DNA and protein bovine serum albumin (BSA) indicates that the complex can interact with herring sperm DNA through the intercalation mode and the binding affinity is dominated by the hydrophobicity and chelate ring arrangement around copper(II) ions and quenches the intrinsic fluorescence of BSA via a static process. The cytotoxicity of the complex shows selective cancer cell antiproliferative activity.     

Metal complexes of naphthoquinone based ligand: synthesis,characterization, protein binding,DNA binding/cleavage and cytotoxicity studies

Protein binding, DNA binding/cleavage and in vitro cytotoxicity studies of 2-((3-(dimethylamino)propyl)amino)naphthalene-1,4-dione (L) and its four coordinated M(II) complexes [M(II) = Co(II), Cu(II), Ni(II) and Zn(II)] have been investigated using various spectral techniques. The structure of the ligand was confirmed by spectral and single crystal XRD studies. The geometry of the complexes has been established using analytical and spectral investigations. These complexes show good binding tendency to bovine serum albumin (BSA) exhibiting high binding constant values (10⁵ M^?1) when compared to free ligand. Fluorescence titration studies reveal that these compounds bind strongly with CT-DNA through intercalative mode (K_app 10⁵ M^?1) and follow the order: Cu(II) > Zn(II) > Ni(II) > Co(II) > L. Molecular docking study substantiate the strength and mode of binding of these compounds with DNA. All the complexes efficiently cleaved pUC18-DNA via hydroxyl radical mechanism and the Cu(II) complex degraded the DNA completely by converting supercoiled form to linear form. The complexes demonstrate a comparable in vitro cytotoxic activity against two human cancer cell lines (MCF-7 and A-549), which is comparable with that of cisplatin. AO/EB and DAPI staining studies suggest apoptotic mode of cell death, in these cancer cells, with the compounds under investigation.     

DNA groove-binding and acid-base properties of a Ru(II) complex containing anthryl moieties

Abstract

DNA groove binders have been poorly studied as compared to the intercalators. A novel Ru(II) complex of [Ru(aeip)₂(Haip)](PF₆)₂ {Haip?=?2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline and aeip = 2-(anthracen-9-yl)-1-ethyl-imidazo[4,5-f][1, 10]phenanthroline} is synthesized and characterized by elemental analysis, ¹H NMR spectroscopy and mass spectrometry. The complex is evidenced to be a calf-thymus DNA groove binder with a large intrinsic binding constant of 10⁶ M^?1 order of magnitude as supported by UV–visible absorption spectral titrations, salt effects, DNA competitive binding with ethidium bromide, DNA melting experiment, DNA viscosity measurements and density functional theory calculations. The acid-base properties of the complex studied by UV–Vis spectrophotometric titrations are reported as well.     

Tumor cytotoxicity of 5,6-dimethyl-1,10-phenanthroline and its corresponding gold(III) complex

A gold(III) complex possessing 5,6-dimethyl-1,10-phenanthroline (5,6DMP) was synthesized and fully characterized using standard spectroscopic techniques, as well as X-ray crystallography and elemental analysis. The complex [(5,6DMP)AuCl₂][BF₄] (2) was found to possess a distorted square planar geometry about the gold(III) center, commonplace for d⁸ Au(III) cations possessing sterically un-hindered polypyridyl ligands. Compound 2 was evaluated for its potential use as an anticancer therapeutic. It was determined that the complex is stable in phosphate buffer over a 24-hour period, thought it does undergo rapid reduction in the presence of equimolar amounts of reduced glutathione (GSH) and ascorbic acid. The DNA binding and in vitro tumor cytotoxicity of the title compound 2 were also determined. It was found to undergo weak and reversible binding to calf thymus DNA, and was more cytotoxic towards a panel of human cancer cell lines than the commonly used chemotherapy agent cisplatin. Cytotoxicity experiments with the free 5,6DMP ligand indicate that the ligand has IC₅₀ values that are slightly lower than those observed for the gold complex (2), and coupled with the fact that the ligand appears to be released from the gold(III) metal center in reducing environments, this suggests the ligand itself may play an important role in the antitumor activity of the parent gold complex.     

New multinuclear Scaffold molybdocene-gold lidocaine complex: DNA/HSA binding,molecular docking,cytotoxicity and mechanistic insights

The new heteronuclear molybdocene-gold complex 1, [(η⁵-Cp)₂Mo^II[(μ²-η²-dtc)₂Nap]Au^III(LC)](PF₆), (η⁵-Cp: η⁵-cyclopentadienyl, (dtc)₂Nap: 2,7-bis(dithiocarbamate)naphthalene, LC: lidocaine) was synthesized and evaluated for biological activity. With the aim of assessing the possible DNA-binding mode, the interaction of the complex 1 with calf thymus DNA (CT DNA) was investigated by UV spectroscopy, emission titration, and viscosity measurement. Also, the binding of the complex to human serum albumin (HSA) was considered by UV–Vis and fluorescence emission spectroscopy. Moreover, molecular docking was used for modeling of the binding of the complex to DNA and HSA. These experimental results were confirmed by the results of molecular docking concerning the lowest binding energy. The cytotoxicity of the heterometallic complex 1 has been evaluated against a panel of several cancer cell lines with low micromolar IC₅₀ (72?h) values, according to its cellular uptake and also versus HEK293 nonmalignant fibroblasts. Moreover, the complex 1 showed the induction of apoptotic process.

Communicated by Ramaswamy H. Sarma     

Synthesis,Structure, DNA‐Binding Properties,and Cytotoxicity of Ruthenium(II) Polypyridyl Complexes

Many ruthenium(II) complexes show high antitumor activities, and the in vitro antitumor activities are usually related to DNA binding. We designed and synthesized two Ru^II polypyridyl complexes, [Ru(dmp)₂(fpp)]²⁺ (dmp=2,9‐dimethyl‐1,10‐phenanthroline; fpp=2‐[3,4‐(difluoromethylenedioxy)phenyl]imidazo[4,5‐f] [1,10]phenanthroline and [Ru(phen)₂(fpp)]²⁺ (phen=1,10‐phenanthroline). The DNA‐binding properties of these complexes have been investigated by spectroscopic titration, DNA melting experiments, viscosity measurements, and photoactivated cleavage. The mechanism studies of photocleavage revealed that singlet oxygen (¹O₂) and superoxide anion radical (O$\rm{{_{2}^{{^\cdot} -}}}$ ) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) method; complex 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened.     

Characteristic effect of an anticancer dinuclear platinum(II) complex on the higher-order structure of DNA

It is known that a 1,2,3-triazolato-bridged dinuclear platinum(II) complex, [{cis-Pt(NH₃)₂}₂(μ-OH)(μ-1,2,3-ta-N ¹,N ²)](NO₃)₂ (AMTA), shows high in vitro cytotoxicity against several human tumor cell lines and circumvents cross-resistance to cisplatin. In the present study, we examined a dose- and time-dependent effect of AMTA on the higher-order structure of a large DNA, T4 phage DNA (166 kbp), by adapting single-molecule observation with fluorescence microscopy. It was found that AMTA induces the shrinking of DNA into a compact state with a much higher potency than cisplatin. From a quantitative analysis of the Brownian motion of individual DNA molecules in solution, it became clear that the density of a DNA segment in the compact state is about 2,000 times greater than that in the absence of AMTA. Circular dichroism spectra suggested that AMTA causes a transition from the B to the C form in the secondary structure of DNA, which is characterized by fast and slow processes. Electrophoretic measurements indicated that the binding of AMTA to supercoiled DNA induces unwinding of the double helix. Our results indicate that AMTA acts on DNA through both electrostatic interaction and coordination binding; the former causes a fast change in the secondary structure from the B to the C form, whereas the latter promotes shrinking in the higher-order structure as a relatively slow kinetic process. The shrinking effect of AMTA on DNA is attributable to the possible increase in the number of bridges along a DNA molecule. It is concluded that AMTA interacts with DNA in a manner markedly different from that of cisplatin.     

Synthesis,DNA/BSA binding studies and in vitro biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands

Abstract

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H₂L¹ = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H₂L² = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O₂˙^? radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H₂L¹ ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC₅₀ value equaled 9.7?μM, which showed potent cytotoxic activity over standard drug cisplatin.

Abbreviations A549 human lung carcinoma cell

BSA bovine serum albumin

CCK-8 Cell Counting Kit-8

DFT density functional theory

DNA deoxyribonucleic acid

DPPH˙ 2,2-diphenyl-1-picrylhydrazyl

H₂L¹ 2-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone

H₂L² N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone

HOMO highest occupied molecular orbital

IC₅₀ the 50% activity

L-02 human normal liver cell

LOMO lowest unoccupied molecular orbital (LUMO)

MCF-7 human breast carcinoma cell

NO˙ nitric oxide

O₂˙^? superoxide anion

SOD superoxide dismutase

Communicated by Ramaswamy H. Sarma