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.     

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.     

Design,synthesis, characterization of zirconium (IV), cadmium (II) and iron (III) complexes derived from Schiff base 2-aminomethylbenzimidazole, 2-hydroxynaphtadehyde and evaluation of their biological activity

(E)-1-((((1H-benzo[d]imidazol-2-yl)methyl)imino)methyl)naphthalen-2-ol, ligand was synthesized by condensation of (1H-benzo[d]imidazol-2-yl) methanamine, with 2-hydroxynaphthaldehyde. The ligand and the metal complexes were characterized by various spectroscopic techniques. Interpretation of spectra confirmed that the ligand adopted either a neutral tridentate or a monobasic tridentate mode, bonded to the metal ions through the nitrogen atom of the heterocyclic benzimidazole, azomethine nitrogen atom and deprotonated phenolic oxygen atom forming either a square planer geometry. X-ray powder diffraction analysis of complexes indicated that the complexes were crystalline in nature with triclinic structures. The antibacterial and the antifungal activities of the ligand and its complexes were examined against Escherichia coli, Bacillus subtilis and Aspergillus niger by well- diffusion method. The results showed that Cd (II) complex exhibits the highest antifungal and antibacterial activities among the tested complexes. The in vitro antitumor activityies of the different complexes were tested and the results revealed an important cytotoxicity of cadmium complex against MCF-7, Hep G2 and HCT 116 cell. Iron complex showed also a strong toxicity towards Hep G2 and HCT cell whereas moderate activity against MCF-7. The bioassay study of different complexes against mosquito larvae demonstrated strong activity of zirconium complex with 0.172 values of LC50.     

Synthesis,characterization, molecular docking studies and in vitro screening of new metal complexes with Schiff base as antimicrobial and antiproliferative agents

A series of Cu(II), Co(II), Pd(II), Pt(II), Zn(II), Cd(II) and Fe(III) complexes were designed and synthesized using Schiff base 1‐phenyl‐2,3‐dimethyl‐4‐(N‐3‐formyl‐6‐methylchromone)‐3‐pyrazolin‐5‐one (HL). The new metal complexes were investigated using various physicochemical techniques including elemental and thermal analyses, molar electric conductivity and magnetic susceptibility measurements, as well as spectroscopic methods. Also, the crystal structures of ligand HL and the Pd(II) complex were determined using single‐crystal X‐ray diffraction analysis. For all compounds, the antimicrobial activity was studied against a series of standard strains: Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis, Escherichia coli, Acinetobacter baumannii, Candida albicans, Candida krusei and Cryptococcus neoformans. The in vitro antiproliferative activity of the ligand and complexes was evaluated against ten cancer cell lines: MSC, A375, B16 4A5, HT‐29, MCF‐7, HEp‐2, BxPC‐3, RD, MDCK and L20B. At 10 μM concentration a significant cytotoxic effect of the Co(II), Pd(II) and Cd(II) complexes was observed against B16 4A5 murine melanoma cells. The Zn(II) complex is active against HEp‐2, RD and MDCK cancer cell lines, where IC₅₀ values vary between 1.0 and 77.6 and for BxPC‐3 the activity index versus doxorubicin is 3.7 times higher.     

A Tri‐copper(II) Complex Displaying DNA‐Cleaving Properties and Antiproliferative Activity against Cancer Cells

A new disubstituted terpyridine ligand and the corresponding tri‐copper(II) complex have been prepared and characterised. The binding affinity and binding mode of this tri‐copper complex (as well as the previously reported mono‐ and di‐copper analogues) towards duplex DNA were determined by using UV/Vis spectroscopic titrations and fluorescent indicator displacement (FID) assays. These studies showed the three complexes to bind moderately (in the order of 10⁴ M ^?1) to duplex DNA (ct‐DNA and a 26‐mer sequence). Furthermore, the number of copper centres and the nature of the substituents were found to play a significant role in defining the binding mode (intercalative or groove binding). The nuclease potential of the three complexes was investigated by using circular plasmid DNA as a substrate and analysing the products by agarose‐gel electrophoresis. The cleaving activity was found to be dependent on the number of copper centres present (cleaving potency was in the order: tri‐copper>di‐copper>mono‐copper). Interestingly, the tri‐copper complex was able to cleave DNA without the need of external co‐reductants. As this complex displayed the most promising nuclease properties, cell‐based studies were carried out to establish if there was a direct link between DNA cleavage and cellular toxicity. The tri‐copper complex displayed high cytotoxicity against four cancer cell lines. Of particular interest was that it displayed high cytotoxicity against the cisplatin‐resistant MOLT‐4 leukaemia cell line. Cellular uptake studies showed that the tri‐copper complex was able to enter the cell and more importantly localise in the nucleus. Immunoblotting analysis (used to monitor changes in protein levels related to the DNA damage response pathway) and DNA‐flow cytometric studies suggested that this tri‐copper(II) complex is able to induce cellular DNA damage.     

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.     

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.     

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.     

Probing of effective pyrazolone based metallonucleases: Molecular docking and in vitro biological critiques

Four novel tryptophan based metal (II) complexes of the type [ML (Try)₂] were prepared by using pyrazolone derived Schiff base ligand. The proposed structure was confirmed by physicochemical methods which reveal octahedral coordination environment around the metal center. Intercalative binding mode of the complexes with CT DNA was confirmed by electronic absorption titration, viscosity measurements and fluorescence spectroscopy. Efficiency of DNA cleavage ability of the metal complexes was explored by the gel electrophoresis technique. The antimicrobial activities of the metal complexes showed potent biocidal activity. The percentage of free radical scavenging activity shows that the complexes are very reactive towards DPPH. Moreover, their cytotoxicity was tested against the two cancer cell lines (MCF‐7 and HepG2) and one normal cell line (NHDF) respectively. The MTT assay shows that the complexes have the anticancer efficacy. Moreover, the complexes exhibit a limited cytotoxicity effect on normal cell line NHDF. The morphological changes of apoptosis cell death were investigated by using Hoechst 33258 staining method. In addition, the Molecular docking studies was executed to consider the nature of binding and binding affinity of the synthesized compounds with DNA (PDB: 1BNA) and protein (PDB: 3hb5).     

Synthesis,crystal structure,DNA interaction and anticancer evaluation of pyruvic acid derived hydrazone and its transition metal complexes

A novel tridentate chelating ligand, Ethyl 2‐(2‐(2‐chlorobenzoyl)hydrazono)propanoate and its late transition metal complexes were synthesized, characterized and evaluated for anticancer behavior. The structures were elucidated with the help of elemental analyses, spectral (vibrational, electronic, NMR and mass) and thermo‐gravimetric techniques. Single crystal X‐ray crystallographic studies of the ligand suggest an orthorhombic lattice structure with Pna21 space group. The interaction of ligand and complexes with DNA (CT‐DNA) has been extensively studied using absorption, emission, viscosity and thermal denaturation studies with E. coli DNA. The DNA cleavage ability of ligand and metal complexes was tested using plasmid pBR322 DNA by gel electrophoresis method. The ligand and its copper complex have been evaluated for their in vitro anticancer activity against human cancer cells of different origin such as KB (Oral), A431 (Skin), Mia‐Pa‐Ca (Pancreases), K‐549 (Lung), K‐562 (Leukemia), MCF‐7 (Breast) and VERO by MTT assay and the apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining method. The studies suggest that ligand and copper complex exhibit significant cytotoxic activity on KB, MCF‐7, A‐431, Mia‐Pa‐Ca‐2 an d A‐549 cell lines compared to K‐562 and VERO cell lines.     

Synthesis and Biological Evaluation of some 3d Metal Complexes with a Novel Heterocyclic Schiff Base

A heterocyclic Schiff base was prepared by condensing 3‐acetylcoumarin with 2‐amino‐3‐carboxyethyl‐4,5,6,7‐tetrahydrobenzo[b ]thiophene. Such Schiff bases derived from two different heterocyclic moieties are rare and expected to have properties surpassing those of either of the parent compounds in effectiveness of complex formation and biological activities. This ligand formed a series of complexes with manganese(II), cobalt(II), nickel(II), copper(II), and zinc(II) ions. The ligand and the metal complexes were characterized by various physicochemical and spectral studies. These included elemental analysis, molar conductance, magnetic susceptibility, as well as UV–vis, IR, ¹H NMR, ¹³C NMR, and ESR spectral studies. The ESR spectral data adequately supported the covalent nature of the metal–ligand bonds. The ligand possessed a hexagonal crystal structure, but on complexation the crystallinity was lost. The fluorescence spectra of the ligand and its metal complexes in DMSO were also recorded. The ligand and the metal complexes were screened for their antimicrobial activities, and it was observed that the metal complexes are more active than the ligand. The α‐amylase inhibitory activity and the DNA cleavage activity of the ligand and the metal complexes were also examined. in vitro antitumor activity of the copper(II) complex was assayed against human cervical carcinoma cells (HeLa cell line), showing that the complex exhibited promising antitumor activity on the HeLa cell line.     

New Ni(II), Pd(II) and Pt(II) complexes coordinated to azo pyrazolone ligand with a potent anti‐tumor activity: Synthesis,characterization, DFT and DNA cleavage studies

The absolute necessity to fight some class of tumor is perceived as serious health concerns, so the discovery and development of effective anticancer agents are urgently needed. (E)‐4‐((2‐hydroxyphenyl)diazenyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one, HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized and the biological activity was evaluated for antitumor, antioxidant and antimicrobial activity as well as DNA cleavage. Their structures were assigned depending on the elemental analysis, conductivity, magnetic moment, spectral measurements (IR, ¹HNMR, mass and UV–Vis) and thermal analysis. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The antitumor activity was evaluated against four different cell lines using MTT assay. The ligand HL showed a potent cytotoxic activity compared to 5‐fluorouracil as a reference drug. For metal complexes, the order of activity was: Pd(II) > Ni(II) > Pt(II). A remarkable antioxidant activity for the ligand HL was recorded. It was higher than that of the metal complexes. Results of antimicrobial experiments revealed that all compounds were moderate to highly active against selected bacterial strains but inactive as antifungal except Pd(II) which showed a moderate antifungal activity. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in the presence of H₂O₂ providing protection of DNA from damage. The antitumor activity of our compounds may be not due to DNA cleavage but may be referred to a mechanism similar to that of 5‐fluorouracil which interfere with DNA replication. The present work suggests the use of this ligand in the design and development of new anticancer drugs.     

RAPTA complexes containing N‐substituted Tetrazole scaffolds: Synthesis,characterization and Antiproliferative activity

This work describes the synthesis of a series of Ru(II)‐Arene (Arene=p‐cymene, benzene) complexes using different N‐substituted tetrazole ligands and their PTA analogues. All the complexes have been characterized thoroughly using different analytical techniques. Antiproliferative activity of the synthesized complexes against different cell lines indicates remarkable activity of certain complexes up to nanomolar level. In few cases introduction of water soluble PTA (PTA = 1,3,5‐ triaza‐7‐phospha‐tricyclo‐[3.3.1.1]decane) ligand induce significant cytotoxic activity in the ruthenium complex with respect to their chloro analogues, particularly against Jurkat and MCF‐7 cell lines. Interaction with different biomolecules and stability of the RAPTA complexes have been explored in pseudo‐pharmacological conditions.     

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.     

Ligational behavior of new mononucleating NOO ethyl pyruvate Schiff base towards 3d metal(II) ions: an emphasis on antiproliferative and photocleavage property

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of a tridentate hydrazone were prepared and characterized by various spectro‐analytical techniques and magnetic moment studies. The complexes were found to be monomeric and non‐electrolytes. The copper complex is electrochemically active in the applied potential range. The compounds synthesized in the present study have shown promising antiproliferative activity when screened using the in vitro method against two human cancer cell lines: HeLa and HepG2. The Escherichia coli DNA‐binding properties of all the compounds were investigated with UV–visible absorption spectrophotometric titrations, viscosity measurements, DNA melting experiments and gel electrophoreses measurements. The compounds were demonstrated to act as DNA intercalators with appreciable DNA‐binding constant values. Copyright © 2012 John Wiley & Sons, Ltd.     

Anticancer Activity of Hydrogen‐Bond‐Stabilized Half‐Sandwich RuII Complexes with Heterocycles

Neutral half‐sandwich organometallic ruthenium(II) complexes of the type [(η⁶‐cymene)RuCl₂(L)] ( H1 – H10 ), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single‐crystal X‐ray diffraction confirming a piano‐stool geometry with η⁶ coordination of the arene ligand. Hydrogen bonding between the N? H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal–ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework ( H1 ) or mercaptobenzoxazole ( H6 ) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1‐phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non‐intercalative fashion and cause unwinding of plasmid DNA in a cell‐free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen‐bond donor on the heterocycle reduces the cytotoxicity.     

Synthesis,structural characterization,antimicrobial, antioxidant and DNA binding studies of some novel homo‐binuclear Schiff base metal (II) complexes

A novel bi‐nucleating Schiff base ligand, 6,6′‐(((1E,1′E)‐thiophene‐2,5‐diylbis (methaneylylidene))bis (azaneylylidene))bis (3,4‐dimethylaniline), and five binuclear M (II) complexes were synthesized. The bi‐nucleating Schiff base ligand and its metal complexes were characterized using various physicochemical techniques, e.g. elemental analyses, spectroscopic methods, conductivity and magnetic moment measurements. The low molar conductance of the complexes in dimethylsulfoxide shows their non‐electrolytic nature. The antibacterial activities were screened against pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas putida and Bacillus subtilis). The antifungal activity was screened against Aspergillus niger, Aspergillus flavus and Rhizoctonia bataicola. The antimicrobial activity data showed that the metal complexes are more potent than the parent Schiff base ligand against microorganisms. The antioxidant activities of the synthesized compounds were investigated through scavenging activity against 2,2‐diphenyl‐2‐picrylhydrazyl, superoxide anion, hydroxyl and 2,2′‐ azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals. The complexes have superior radical scavenging activity than the free ligand and the scavenging effects of the Cu (II) complex are stronger than those of the other complexes. DNA binding studies were performed using electronic spectroscopy, fluorometric competition studies and viscosity measurements. The data indicated that there is a marked enhancement in biocidal activity of the ligand under similar experimental conditions because of coordination with metal ions.     

Synthesis,characterization and catalytic,cytotoxic and antimicrobial activities of two novel cyclotriphosphazene‐based multisite ligands and their Ru(II) complexes

Two novel cyclotriphosphazene ligands ( 2 and 3 ) bearing 3‐oxypyridine groups and their corresponding Ru(II) complexes ( 4 and 5 ) were synthesized and their structures were characterized using Fourier transform infrared, ¹H NMR and ³¹P NMR spectroscopic data and elemental analysis. The Ru(II) complexes were used as catalysts for catalytic transfer hydrogenation of p‐substituted acetophenone derivatives in the presence of KOH. Additionally, the cytotoxic activities of compounds 2 , 3 , 4 , 5 were evaluated against PC3 (human prostate cancer), DLD‐1 (human colorectal cancer), HeLa (human cervical cancer) and PNT1A (normal human prostate) cell lines. Finally the antimicrobial activities of compounds 2 , 3 , 4 , 5 were evaluated against a panel of Gram‐positive and Gram‐negative bacteria and yeast cultures. The complexes showed efficient catalytic activity towards transfer hydrogenation of acetophenone derivatives, especially those bearing electron‐withdrawing substituents on the para‐position of the aryl ring. The compounds were found to have moderate to high cytotoxic and antimicrobial activities, and Ru(II) complexation enhanced both cytotoxic and antimicrobial activities in comparison with the parent compounds. Copyright © 2015 John Wiley & Sons, Ltd.     

Coordination compounds of some transition metal ions with new Schiff base ligand derived from dibenzoyl methane. Structural characterization,thermal behavior,molecular structure,antimicrobial, anticancer activity and molecular docking studies

Series of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes were prepared with tetradentate Schiff base ligand derived by condensation of 2‐aminophenol with dibenzoylmethane. The novel Schiff base H₂L (2–2′‐((1Z,1Z’)‐(1,3‐diphenyl propane‐1,3 diylidene) bis (azanylylidene) diphenol) and its binary metal complexes were characterized by physicochemical procedures i.e. elemental analysis, FT‐IR, UV–Vis, thermal analyses (TGA/DTG), mass spectrometry, magnetic susceptibility and conductometric measurements. On the basis of these studies, an octahedral geometry for all these complexes was proposed expect Ni(II) complex which had tetrahedral geometry. Molar conductivity values revealed that the complexes were electrolytes except Mn(II), Zn(II) and Cd(II) complexes were non electrolytes. The ligand bound to the metal ions via two azomethine N and two phenolic OH as indicated from the IR and ¹H NMR spectral study. The molecular and electronic structures of H₂L and its zinc complex were optimized theoretically and the quantum chemical parameters were calculated. The antimicrobial activity against a number of bacterial organisms as Streptococcus pneumonia, Bacillus Subtilis, Pseudomonas aeruginosa and Escherichia coli and fungi as Aspergillus fumigates, Syncephalastrum racemosum, Geotricum candidum and Candida albicans by disk diffusion method were screened for the Schiff base and its complexes. The Cd(II) complex has potent antimicrobial activity. Anticancer activity of the Schiff base ligand and its metal complexes were evaluated in human cancer (MCF‐7 cells viability). The Cr(III) complex exhibited higher activity than other complexes and ligand. Molecular docking was used to predict the binding between Schiff base ligand (H₂L) and its Zn(II) complex and the receptors of RNA of amikacin antibiotic (4P20) and human‐DNA‐Topo I complex (1SC7). The docking study provided useful structural information for inhibition studies.     

Some new Ag(I), VO(II) and Pd(II) chelates incorporating tridentate imine ligand: Design,synthesis, structure elucidation,density functional theory calculations for DNA interaction,antimicrobial and anticancer activities and molecular docking studies

Some new complexes derived from VO(II), Ag(I) and Pd(II) metal ions and HNA imine ligand (L), i.e. (2‐((6‐allylidene‐2‐hydroxycyclohexa‐1,3‐dienylmethylene)amino)benzoic acid), have been prepared and their structures elucidated via molar conductance measurements, elemental analyses, infrared, NMR and electronic spectra and magnetic susceptibility estimations. Moreover, stability constants of the synthesized complexes were evaluated utilizing a spectrophotometric technique. On the basis of molar conductance and elemental analyses, the metal imine chelates have structure [M(L)], where M = Pd(II), VO(II) and Ag(I). The results indicate that the prepared HNA imine ligand acts as a tridentate moiety via nitrogen atom of azomethine group and two oxygen atoms of phenolic and carboxylic groups. All the complexes are found to be monomeric with 1:1 stoichiometry with square planar geometry for Pd(II), tetrahedral geometry for Ag(I) and distorted square pyramidal for VO(II). Theoretical density functional theory calculations were applied to verify the molecular geometry of the chelators and their metal chelates. The geometry optimization results are in agreement with experimental observations. The antimicrobial properties of the prepared HNA imine ligand and its metal chelates were evaluated against numerous plant pathogenic fungi and bacteria. The results of these studies indicate that the metal complexes exhibit a stronger antibacterial and antifungal effect compared to the imine ligand. In addition, the interaction of the metal imine chelates with calf thymus DNA was observed by way of viscosity, gel electrophoreses and spectral studies. Absorption titration studies reveal that each of the complexes is an avid binder to calf thymus DNA. Also, there are appreciable changes in the relative viscosity of DNA, which are consistent with enhanced hydrophobic interaction of the aromatic rings and intercalation mode of binding. Additionally, the cytotoxic activity of the investigated compounds against various cancer cell lines shows promising results which makes them prospective compounds for antibiotic and anticancer medicament studies. Furthermore, docking studies of the prepared compounds were conducted for confirming the biological results.