Antibacterial and Superoxide Dismutase Activity as Well as DNA Interactions of Ciprofloxacin‐Based Ternary Copper(II) Phenanthroline Complexes

. Five neutral mixed‐ligand mononuclear square‐pyramidal copper(II) complexes of the type [Cu(cpf)(Lⁿ)Cl] (cpf = ciprofloxacin and Lⁿ = phenanthroline derivatives) ( 1 – 5 ) were synthesized and characterized. The complexes were screened for their antibacterial activity and bactericidal activity against two Gram^(+ve) and three Gram^(–ve) microorganisms and the results showed that all complexes studied are more potent than the quinolone standard drug ciprofloxacin. Absorption titration, viscosity, and thermal denaturation measurement studies revealed that each of these square‐pyramidal complexes moderately interacts with calf thymus DNA. The binding constants for mixed ligand complexes are in order of 1.5 × 10⁴–3.0 × 10⁴ M^–1. Based on the data obtained in the DNA binding studies an intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of adducts and gyrase inhibition assay were studied on double stranded pUC19 DNA by gel electrophoresis experiments. From the SOD mimic study; the concentration of complexes ranging from 0.45 μM to 1.45 μM are enough to inhibit the reduction rate of NBT by 50 % (IC₅₀) in NADH/PMS system.     

Synthesis,characterization, antimicrobial,SOD mimic and DNA interaction behavior of copper(II) complexes with pefloxacin and phenanthroline derivatives

Square pyramidal copper(II) complexes with second‐generation fluoroquinolone, pefloxacin and phenanthroline derivatives were prepared and characterized. They were also screened for in–vitro activity against two Gram^(+ve) and three Gram^(−ve) microorganisms. SOD mimic behavior was actively sought for clinical and mechanistic purposes under a nonenzymatic system (NBT–NADH–PMS), and was found to have good antioxidant activity. The complexes are avid DNA binders having binding constant (K_b) in the power of 4. Viscosity measurement data confirmed that complexes bind through classical intercalative mode of binding. The cleavage ability on pUC19 DNA was determined using gel electrophoresis technique. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis, Characterization, and Antibacterial Activity of Complexes of (1S,2S)-N,N-1,2-Diphenylethylene- bis -(5-imino-1-phenyl-1,3-hexanedione)

 The synthesis and characterization of homobimetallic complexes of VO(IV), Cr(II), Co(II), Ni(II), and Cu(II) with the chiral Schiff base (1S,2S)-N,N-1,2-Diphenylethylene-bis-(5-imino-1-phenyl-1,3-hexa-nedione) is reported. The metal ions occupy both compartments of the ligand; water molecules fill the coordination spheres to provide an octahedral environment around the central atoms. The antibacterial activity of both mono- and bimetallic complexes against a number of Gram-positive as well as Gram-negative bacteria has been tested and is discussed.     

Synthesis,characterization and biological application of cyclometalated heteroleptic platinum(II) complexes

A series of square planar cyclometalated heteroleptic platinum(II) complexes of the type [(C^N)Pt(O^O)] [where, O^O is a β‐diketonato ligand of acetylacetone (acac), C^N = cyclometalating 7‐(4‐fluorophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L¹), 7‐(4‐chlorophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L²), 7‐(4‐bromophenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L³), 7‐(4‐methoxyphenyl)‐5‐phenylpyrazolo[1,5‐a]pyrimidine (L⁴), 5‐phenyl‐7‐(p‐tolyl)pyrazolo[1,5‐a]pyrimidine (L⁵)] have been design, synthesized and characterized. All compounds have been screened for biological studies like in vitro antibacterial, in vitro cytotoxicity, cellular level cytotoxicity, absorption titration, viscosity measurements, fluorescence quenching analysis, molecular docking and DNA nuclease. The intrinsic binding constants (K_b) of compounds with HS‐DNA has been obtained in range of 2.892–0.242 × 10⁵ M^?1. All the compounds bound with HS DNA by partial intercalative mode of binding. MIC study has been carried out against Gram^(+ve) and Gram^(?ve) bacterial species. In vitro cytotoxicity against brine shrimp lethality bioassay has been also carried out. The LC₅₀ values of the ligands and complexes have been found in range of 56.49–120.22 μg/mL and 6.71–11.96 μg/mL, respectively.     

Synthesis, Characterization, and Antibacterial Activity of Complexes of (1S,2S)-N,N-1,2-Diphenylethylene-bis-(5-imino-1-phenyl-1,3-hexanedione)

Summary.  The synthesis and characterization of homobimetallic complexes of VO(IV), Cr(II), Co(II), Ni(II), and Cu(II) with the chiral Schiff base (1S,2S)-N,N-1,2-Diphenylethylene-bis-(5-imino-1-phenyl-1,3-hexa-nedione) is reported. The metal ions occupy both compartments of the ligand; water molecules fill the coordination spheres to provide an octahedral environment around the central atoms. The antibacterial activity of both mono- and bimetallic complexes against a number of Gram-positive as well as Gram-negative bacteria has been tested and is discussed. Received March 28, 2000. Accepted May 26, 2000     

FT-Raman,FT-IR,NMR structural characterization and antimicrobial activities of 1,6-bis(benzimidazol-2-yl)-3,4-dithiahexane ligand and its Hg(II) halide complexes

1,6-Bis(benzimidaz-2-yl)-3,4-dithiahexane ligand (L) and its mercury halide complexes were prepared and characterised. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid, far), ¹H, ¹³C NMR and geometry optimization in MOPAC using MNDOd parameter on CACHE, prove the existence of neutral, mononuclear and the distorted tetrahedral [Hg(L)X₂] complexes. In all the three complexes, the ligand acts as a chelating bidentate, through two of the bridging sulphur atoms and together with the monodentate coordination of the two anionic halide ligands to the metal centre forming a possible 4-coordinate compounds. The antimicrobial activities of free ligand, its hydrochlorinated salt, mercury halides and the complexes are evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria. The obtained results from disk diffusion method are assessed in side-by-side comparison with those of Penicillin-g, Ampicillin, Cefotaxime, Vancomycin, Oflaxacin and Tetracyclin well-known antibacterial agents. The results from dilution procedure are compared with Gentamycin as antibacterial and Nystatin as antifungal. The antifungal activities are reported on five yeast cultures namely Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii and Hanseniaspora guilliermondii, and the results are referenced with Nystatin, Ketaconazole and Clotrimazole, commercial antifungal agents. In most cases, the compounds show broad-spectrum (Gram⁺ & Gram⁻ bacteria) activities that are comparatively, slightly less active or equipotent to the antibiotic and antifungal agents in the comparison tests.     

A convenient, rapid and eco-friendly synthesis of isoxazoline heterocyclic moiety containing bridge at 2°-amine as potential pharmacological agent

2-Amino-4-(coumarin-3-yl)-thiazole (1) reacted with acetyl chloride gives compound (2) which on further refluxed with various aromatic aldehydes gives compound (3a-j). Thus obtained (3a-j) on further condensed with NH₄OH.HCl using NaOH as a catalyst afforded isoxazoles (4a-j). All the synthesized compounds characterized on the basis of the IR, ¹H NMR, ¹³C NMR and elemental analysis. All the compounds have been screened for antibacterial activity against bacteria (Gram + ve) & (Gram ? ve) and antifungal activity.     

In-vitro antibacterial activity of Ni(II), Cu(II), and Zn(II) complexes incorporating new azo-azomethine ligand possessing excellent antioxidant,anti-inflammatory activity and protective effect of free radicals against plasmid DNA

Azo Schiff base ligand 2-hydroxy-3-methoxy-5-(tolyldiazenyl)benzaldehyde oxime (HL¹) and 2-hydroxy-3-methoxy-5-(methoxyphenyl)benzaldehyde oxime (HL²) were prepared along with their transition metal complexes of Ni(II), Cu(II), and Zn(II). Ligands and their metal complexes were characterized by several analysis techniques. In- vitro antibacterial, antioxidant and anti-inflammatory activities of synthesized ligands and their metal complexes have been studied. Biological study showed that amongst all the synthesized compounds, Cu(II) complexes possessed excellent antibacterial activity than standard antibiotic Chloramphenicol. Ligands (HL¹) and (HL²) showed excellent antioxidant as well as anti-inflammatory activity. Both the ligands were tested for their protective effect of free radicals against plasmid DNA and it was found that both the ligands showed good DNA nicking activity.     

Novel 3‐Hydroxy‐2‐naphthoic hydrazone and Ni(II), Co(II) and Cu(II) Complexes: Synthesis,Spectroscopic Characterization,Antimicrobial, DNA Cleavage and Computational Studies

A novel hydrazone ligand derived from condensation reaction of 3‐hydroxy‐2‐naphthoic hydrazide with dehydroacetic acid, and its Ni(II), Cu(II) and Co(II) complexes were synthesized, characterized by spectroscopic, elemental analyses, magnetic susceptibility and conductivity methods, and screened for antimicrobial, DNA binding and cleavage properties. Spectroscopic analysis and elemental analyses indicated the formula, [MLCl₂], for the complexes; square planar geometry for the nickel, and tetrahedral geometry for copper and cobalt complexes. The non‐electrolytic natures of the complexes in Dimethyl Sulphoxide (DMSO) were confirmed by their molar conductance values in the range of 6.11–14.01 Ω^?1cm²mol^?1. The copper complex had the best antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA, by agarose gel electrophoresis, in the presence and absence of oxidant (H₂O₂) and free radical scavenger (DMSO), indicated no activity for the ligand, and moderate activity for the complexes, with the copper complex cleaving pBR322 DNA more efficiently in the presence of H₂O₂. When the complexes were evaluated for antibacterial and A‐DNA activity using Molecular docking technique, the copper complex was found to be most effective against Gram‐positive (S. aureus) bacteria. [CuLCl₂] showed good hydrogen bonding interaction with the major‐groove (C₂^.G₁₃ base pair) of A‐DNA. Density functional theory (DFT) calculations of the structural and electronic properties of the complexes revealed that [CuLCl₂] had a smaller HOMO‐LUMO gap, suggesting a higher tendency to donate electrons to electron‐accepting species of biological targets.     

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.     

Stereoselective Synthesis,Characterization, and Antibacterial Activities of Novel Isosteviol Derivatives with D‐Ring Modification

Considerable interests have been attracted by isosteviol and its derivatives because of their large variety of bioactivities. In this project, a series of novel 15‐ and 16‐substituted isosteviol derivatives were stereoselectively prepared by means of functional interconversions in ring D of the tetracyclic diterpene isosteviol. All compounds synthesized were characterized by analysis of NMR, IR, HR‐MS data, and the configurations of 33 and 37 were confirmed by X‐ray crystallographic analysis. The antibacterial activities in vitro of these isosteviol derivatives were investigated; the synthetic compounds were more active against Gram‐positive than Gram‐negative bacteria, and were especially active against Bacillus subtilis. Among them, compound 27 (MIC=1.56 μg/ml) exhibited the highest antibacterial activity and thus may be exploitable as a lead compound for the development of potent antibacterial agents.     

DNA interaction,antimicrobial and molecular docking studies of biologically interesting Schiff base complexes incorporating 4‐formyl‐N,N‐dimethylaniline and propylenediamine

Four new transition metal complexes incorporating a Schiff base ligand derived from propylenediamine and 4‐formyl‐N ,N ‐dimethylaniline have been synthesized using transition metal salts. The characterization of the newly formed complexes was done from physicochemical parameters and using various techniques like ¹H NMR, ¹³C NMR, IR, UV, electron paramagnetic resonance and mass spectroscopies, powder X‐ray diffraction and magnetic susceptibility. All the complexes were found to be monomeric in nature with square planar geometry. X‐ray powder diffraction illustrates that the complexes have a crystalline nature. The interaction of metal complexes with calf thymus DNA was investigated using UV–visible absorption, viscosity measurements, cyclic voltammetry, emission spectroscopy and docking analysis. The results indicate that the Cu(II), Co(II), Ni(II) and Zn(II) complexes interact with DNA by intercalative binding mode with optimum intrinsic binding constants of 4.3 × 10⁴, 3.9 × 10⁴, 4.7 × 10⁴ and 3.7 × 10⁴ M⁻¹, respectively. These DNA binding results were rationalized using molecular docking in which the docked structures indicate that the metal complexes fit well into the A‐T rich region of target DNA through intercalation. The metal complexes exhibit an effective cleavage with pUC19 DNA by an oxidative cleavage mechanism. The synthesized ligand and the complexes were tested for their in vitro antimicrobial activity. The complexes show enhanced antifungal and antibacterial activities compared to the free ligand.     

New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Herein, we report the synthesis of eight new mononuclear and binuclear Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn²⁺-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu²⁺ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.     

Nickel versus copper: enhanced antibacterial activity in a series of new nickel(II) Schiff base complexes

Five new Ni(II) Schiff base complexes [NiL^x(Solv)₂] denoted by NiL^x, x = 1–5, were synthesized and characterized. The Schiff base ligands were synthesized from the condensation of 5-bromo-2-hydroxy-3-nitrobenzaldehyde with different aliphatic and aromatic diamines. The X-ray crystal structure of NiL³ was determined. The ligands and complexes were tested as antibacterial agents against two gram(+) and two gram(?) human pathogenic bacteria. The complexes showed moderate antibacterial activity against both gram type bacteria. The new Ni(II) complexes showed enhanced antibacterial activity compared to the previously reported Cu(II) complexes of the same ligands.     

Synthesis,spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

Seven new copper(II) complexes of type [Cu(A)(L)]?H₂O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (K_b = 1.27–3.13 × 10⁵ M^?1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC₅₀ values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC₅₀ values ranging from 5.559 to 11.912 µg ml^?1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC₅₀ = 0.62–2.0 µg ml^?1). Copyright © 2015 John Wiley & Sons, Ltd.     

Spectroscopic and thermal investigations of transition and non-transition metal complexes of penicillin G as potential biological active species

Seven types of complexes were obtained when penicillin G potassium (pin) was reacted with transition and non-transition metal ions in methanol/distilled water mixed solvent. Magnetic susceptibilities and ESR spectra (Cu^II complex) of powdered samples indicated that the monomeric form of the complexes in the solid state, and the paramagnetic nature of the Cu^II, Ni^II, Mn^II, Cr^III, Co^II, and Fe^III complexes is attributable to the octahedral ligitional behavior of the potassium G penicillinate ligand. The antibacterial activity of the metal complexes were tested against some kind of bacteria and fungi strains and compared with penicillin G potassium activity. The possible mechanism of antibacterial action is discussed.     

DNA binding and antibacterial properties of ternary lanthanide complexes with salicylic acid and phenanthroline

Twelve ternary lanthanide complexes RE(sal)₃phen (RE³⁺ = La³⁺, Pr³⁺, Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Ho³⁺, Tm³⁺, Yb³⁺, Lu³⁺, sal = salicylic acid, phen = phenanthroline) were prepared. Interactions between the complexes and calf thymus DNA (ct‐DNA) were investigated using UV–visible spectrophotometry, fluorescence quench experiment and viscosity measurement. Hypochromicity and red shift of the absorption spectra of complexes were observed in the presence of DNA. The enhanced emission intensity of ethidium bromide (EB) in the presence of DNA was quenched by the addition of lanthanide complexes, which indicated that the lanthanide complexes displaced EB from its binding sites in DNA. Based on the systematic research of the binding constant (K_b) and the fluorescence quenching constant (K_q) of the 12 complexes, we found that the complexes with smaller lanthanide ion radius had stronger binding abilities with DNA. Viscosity measurement showed that the relative viscosity of the DNA solution was enhanced with increasing the amounts of the complexes. All these results suggested that the complexes could bind to DNA and the major binding mode was intercalative binding. Moreover, all these complexes exhibited excellent antibacterial abilities against Escherichia coli. Also, the antibacterial activities of complexes with heavy rare earth were higher than those of complexes with light rare earth. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis,Characterization, and Biological Evaluation as Antibacterial Agents of Water‐Soluble Calix[4]arenes and Phenol Derivatives Incorporating Carboxylate Groups

As part of specific investigations dedicated to the building of a chemical library of calixarenes with anti‐infective properties, some H₂O‐soluble calix[4]arene derivatives incorporating carboxylate groups at the upper rim and heterocycles at the lower rim have been prepared and characterized as have their constitutive functional monomers. In vitro antibacterial testing against Gram‐positive and Gram‐negative reference strains shows that the derivative with two 5,5′‐dicarboxylated 2,2′‐bithiazole subunits in alternate positions at the lower rim displays an activity at ca. 70 μM (128 μg/ml) on S. aureus ATCC 29213.     

Dicoumarol complexes of Cu(II), Fe(II) and Fe(III): preparation,characterization, in‐vitro antibacterial and DNA binding activity

3‐3′‐Benzylidenebis[4‐hydroxycoumarin] or 4‐nitro,3‐3′‐benzylidenebis[4‐hydroxycoumarin] or 4‐methoxy,3‐3′‐benzylidenebis[4‐hydroxycoumarin] and their complexes with Cu(II), Fe(II) and Fe(III) were synthesized and characterized using ¹H‐NMR, ¹³C‐NMR, IR spectra, electronic spectra, magnetic measurements and elemental analyses. The ligands, metal salts, complexes, control and standard drug were tested for their in‐vitro antibacterial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Serratia marcescens. The metal complexes exhibit good activity against bacterial strains compared with parental compounds and moderate compared with the standard drug (ciprofloxacin). In‐vitro DNA‐binding activity was carried out using agarose gel electrophoresis. The synthesized compounds show effective DNA‐binding activity. Copyright © 2007 John Wiley & Sons, Ltd.