Synthesis,in Vitro and in Vivo Antitumor and Antimicrobial Activities of a Novel Schiff Base Ligand, (e)-ethyl-3-((2-((e)-(2-Hydroxybenzylidene)Amino)Ethyl)Imino)Butanoate and its Transition Metal Complexes

Pharmaceutical Chemistry Journal - Neutral tetradentate N2O2 type complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) have been synthesized using a mixed Schiff base ligand formed by...     

Synthesis, spectroscopic, thermal and antimicrobial studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

Coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with Schiff base derived from syringaldehyde and 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine have been synthesized. These complexes have been characterized by elemental analysis, magnetic moment, spectroscopic (IR, Electronic, ¹H NMR, ESR) and thermogravimetric analysis. Magnetic and spectral data suggest octahedral geometry for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. The presence of coordinated water in metal complexes was confirmed by thermal and IR data. The Schiff base and its metal complexes have been screened for antibacterial (Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, Staphylococcus aureus) and antifungal activities (Aspergillus niger, A. flavus). A comparison is made between activities of complexes with Schiff base and with the standard antibiotics.     

Synthesis and biological activity of mixed ligand dioxouranium(VI) and thorium(IV) complexes

Mixed ligand complexes of dioxouranium(VI) and thorium(IV) in the proportion 1:1:1 and 1:2:1 have been synthesized using 8-hydroxyquinoline as a primary ligand and L-proline and 4-hydroxy-L-proline as secondary ligands, respectively. The metal complexes have been characterized on the basis of elemental analysis, molar conductance, magnetic, spectral and thermal studies. The molar conductance studies of the complexes in DMF at 10(-3) M concentrations indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. The thermal analysis data of the complexes indicates the presence of a coordinated water molecule/molecules. The tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria Staphylococcus aureus and Escherichia coli. The results have been compared against those of control tetracycline, which was screened simultaneously. The complexes have been screened for in vitro cytotoxicity (IC50) studies against Ehrlich ascites cells and Dalton's lymphoma ascites cells, respectively.     

Antibacterial and antifungal oxovanadium(IV) complexes of triazole-derived Schiff bases

A newly synthesised series of antibacterial and antifungal triazole-derived Schiff base ligands (L ¹ )–(L ⁵ ) has been prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with methyl-, chloro- and nitro-substituted thiophene-2-carboxaldehydes in (1:2) molar ratio. The most probable structures of the synthesised Schiff base ligands were established on the basis of their physical, spectral (IR, ¹H and ¹³C NMR and mass spectrometry) and analytical (CHN analysis) data. These Schiff bases potentially act as bidentate ligand and were further made to react with the vanadyl(IV) sulphate (VOSO₄·5H₂O) in (1:2) (metal:ligand) molar ratio to prepare their oxovanadium(IV) complexes (1)–(5). All oxovanadium(IV) complexes showed a square-pyramidal geometry which was established on the basis of their physical, spectral and analytical data. The Schiff base ligands and their vanadyl(IV) complexes have been screened for their in vitro antibacterial, antifungal and brine shrimp bioassay. The antimicrobial activity data showed the vanadyl(IV) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Synthesis, characterization, and antibacterial activity of a novel heterocyclic Schiff’s base and its metal complexes of first transition series

The synthesis of a series of some novel Schiff base complexes of Cu(II), Ni(II), Co(II), Mn(II), Zn(II) with a tetradentate Schiff base has been achieved by the reaction of malonyl hydrazide with dehydroacetic acid in ethanol under refluxing condition. All the synthesized metal complexes and ligand were characterized on the basis of elemental analysis, UV–Visible, ¹H and ¹³C NMR, IR spectroscopy and mass spectrometry. The IR spectral data suggest that azomethine N and enolic O atom are involved in coordination with metal ions, and the ligand behaves as a tetradentate ligand with ONNO donor atoms. The mass spectrum of the complexes reveals the formation of metal ligand bonding in stoichiometric ratio 1:1 (M:L). The UV–Visible data suggest the square planner geometry for the synthesized complexes. All compounds were screened for their antibacterial activity against gram-positive and gram-negative bacteria using Ampicillin as a standard drug. It has been found that metal complexes show enhanced activity as compared to ligand, and some modification in ligand structure may lead to better antibacterial agents in future.     

Speciation of bioactive Al(III) and VO(IV) complexes in biological systems

The speciation of the toxic Al(III) and the beneficial VO(IV) in various biofluids and tissues is discussed in order to describe the solution state of these metal ions in the organism. The possibility and the importance of ternary complex formation with relevant biomolecules is emphasised. The importance of the biospeciation of Al(III) ion in its transport and involvement in neurological disorders, and of insulin mimetic VO(IV) complexes is discussed.     

Synthesis, characterization, antibacterial and cytotoxicity studies on some mixed ligand Th(IV) complexes

Mixed ligand Th(IV) complexes of the type [M(Q)2LNO3.H2O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-alanine, L-phenylalanine, L-serine and L-tyrosine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in DMF at 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. The thermal analysis data of the complexes indicate the presence of a coordinated water molecule. The tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus and E. coli. The results have been compared against those of control tetracycline, which was screened simultaneously and indicate mild antibacterial activity of the complexes. The representative complex has been screened for cytotoxicity (IC50) studies against Ehrlich ascites cells and Daltons lymphoma ascites cells and shows low cytotoxic activity.     

Antimicrobial and antioxidant activities of new metal complexes derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol

(E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol (LH) has been synthesized and used as a ligand for the formation of V(IV), Cr(III), Mn(II), Co(II), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes have the general formula [ML₂(H₂O)₂] [where M?=?Mn(II), Co(II), and Cu(II)], while the Cr(III) complex has the formula [CrL₂(H₂O)₂]Cl, V(IV) complex has the formula [VO₂L₂], and Ni(II) complex has the formula [NiL₂]. The molar conductance data revealed that all the metal chelates except the Cr(III) are non-electrolytes. From the magnetic susceptibility measurement and UV–Visible spectra, it is found that the structures of Cr(III), Mn(II), Co(II), and Cu(II) complexes are octahedral, V(IV), complex is square pyramid and Ni(II) complex is square planar. The stability of the prepared complexes was studied theoretically using density function theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by their interaction with the stable DPPH-free radicals. All the compounds have shown encouraging antioxidant activities.     

Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands L¹H₃ and L²H have been prepared. The ligands are synthesized by the condensation of 2-hydroxy-3-formylquinoline with salicyloylhydrazide and 2-hydrazinobenzothiazole in absolute ethanol. The prepared complexes were characterized by the analytical and spectral techniques. The stoichiometry of the complexes is found to be 1:1. The presence of coordinated and lattice water is confirmed by the TG and DTA studies. Subsequently all the prepared complexes were screened for antimicrobial activity against bacteria and fungi. The Cu(II) complexes have been found to be more active than the ligand. In addition the DNA binding/cleaving capacity of the compounds was analyzed by absorption spectroscopy, viscosity measurement, thermal denaturation, and gel electrophoresis methods.     

DNA cleavage and antimicrobial investigation of Co(II), Ni(II), and Cu(II) complexes with triazole Schiff bases: synthesis and spectral characterization

The Co(II), Ni(II), and Cu(II) complexes with Schiff bases derived from 3-substituted-4-amino-5-mercapto-1,2,4-triazole and fluvastatin have been synthesized. Schiff bases exhibited thiol–thione tautomerism and coordinated to metal ion through azomethine nitrogen and thiolate sulphur atoms. Square planar geometry for all the metal complexes of the type ML₂ has been proposed in the light of analytical, spectral (IR, UV–Vis., ESR, and FAB-mass), magnetic, and thermal studies. The antimicrobial studies of Schiff bases and their metal complexes against various antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis) and antifungal (Aspergillus niger, and Pencillium Chrysogenum) species by Minimum Inhibitory Concentration method revealed that, the metal complexes possess more healing antibacterial activity than the Schiff bases. Co(II), Ni(II), and Cu(II) complexes cleave the DNA isolated from A. niger.     

Preparation, X-ray structural and spectroscopic studies of some D-lactobionic acid complexes with Cs(I), Fe(III) and di-n-butyltin(IV)

D-Lactobionic acid (4-O-beta-D-galactopyranosyl-D-gluconic acid) complexes of Cs(I), Fe(III) and di-n-butyltin(IV)2+ ions were prepared in the solid state. The bonding sites of the ligands were verified by means of FTIR, Raman and 13C NMR spectroscopic measurements. The Cs(I)-D-lactobionate was obtained in single-crystal form. The X-ray crystallographic results on Cs(I)-D-lactobionate demonstarted that each Cs(I) ion is bonded to four D-lactobionate ions, forming an intricate 3D network. The asymmetric unit consists of one Cs(I), one D-lactobionate ion and one water molecule. For the di-n-butyltin(IV) complex, M?ssbauer pqs calculations indicated octahedral and trigonalbipyramidal stereochemistry around the central tin atom in the oligomeric compound. In DMSO solution, the polymeric structure does not remain as shown by 13C NMR measurement. One solvent molecule is coordinated additionally to the tin center, and the carboxylate group has become monodentate. According to the EPR measurement, the Fe(III) complexes obtained at different pH have at least dimeric or oligomeric structure.     

Synthesis, Characterization and Biocidal Activities of Some Schiff Base Metal Complexes

Some new mixed ligand complexes (1-5) of type ML''B (M(II)=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); HL''= o-vanillidene-2-aminobenzothiazole; B= 1,10-phenanthroline) and Schiff base metal complexes of types (ML₂") (6-10) and (M₂L") (11-15) (HL"= o-vanillidene-2-amino-N-(2-pyridyl)-benzene sulfonamide) were synthesized and characterized by elemental analysis and spectral (IR, ¹H NMR and ¹³C NMR) studies. The free ligands and their metal complexes have been screened for their in vitro biological activities against bacteria, fungi and yeast. The metal complexes show more potent activities compared with Schiff base ligands.     

Lipophilicity of kinetically labile metal complexes through the example of antidiabetic Zn(II) and VO(IV) compounds

The lipophilic character of several carrier ligands of antidiabetic Zn(II) and VO(IV) metal complexes were characterized by the traditional saturation shake flask method based on n-octanol/water partitioning. The transfer of the neutral ligand species to the organic phase was followed by UV spectrophotometry at various pH and the partition and distribution coefficients were calculated with the help of the proton dissociation constants and the spectra of the individual ligand species. Partition and distribution coefficients of the Zn(II) and VO(IV) complexes were determined by analysis of the metal ion content of the aqueous phases before and after separation by ICP-AES, their UV spectra and the corresponding concentration distribution curves. Results revealed the fairly hydrophilic character both the carrier ligands and their neutral Zn(II) and VO(IV) complexes. A quasi-linear relationship was found between logP of the ligands and that of the metal species in the case of the ligands studied with the exception of the picolinates. Importance of the knowledge of the chemical speciation (i.e. stoichiometry and stability constants) was also highlighted for the characterization of the lipophilic character of the kinetically labile metal complexes.     

Transition metal complexes of s-triazine derivative: new class of anticonvulsant, anti-inflammatory, and neuroprotective agents

A new series of transition metal complexes of 2,4-bis(indolin-3-one-2-ylimino)-6-phenyl-1,3,5-triazine) (BIPTZ) have been synthesized. The structural features of BIPTZ and metal(II) complexes were investigated using elemental analyses, magnetic susceptibility, molar conductance, mass, IR, UV–Vis, ¹H NMR, ¹³C NMR, CV, and ESR spectral studies. Electronic absorption spectra and magnetic susceptibility measurements of the complexes predict their geometry. The redox behavior of the copper(II) complexes has been studied by cyclic voltammetry. All the synthesized compounds may serve as potential photoactive materials as indicated from their characteristic fluorescence spectrum. The Schiff base and its metal complexes were screened for anticonvulsant and anti-inflammatory activities in vivo. The metal(II) complexes are potent agents in treating neurochemical and behavioral abnormalities seen in Parkinson’s diseased (PD) mice than free ligand.     

Effects of metal salophene and saldach complexes on lymphoma and leukemia cells

Schiff base transition metal complexes are an important class of compounds with great potential for therapeutic interventions. However, data on antileukemic and antilymphoma effects of these complexes are limited. The activity of N,N'-bis(salicylidene)-1,2-phenylenediamine (salophene, 1), its iron(II/III) and manganese(II/III) complexes as well as rac-trans-N,N'-bis(salicylidene)-1,2-cyclohexanediamine (saldach, 2) and its respective iron(II/III) complexes was evaluated against U-937 non-Hodgkin's lymphoma and the HL-60, SUP-B15, and K-562 leukemia cell lines. The free ligands induced in all cell lines, if at all, only marginal, concentration-dependent growth inhibitory effects, and did not trigger Cu/Zn superoxide dismutase (Cu/Zn SOD) release or induce apoptosis. [Fe(II) (salophene)] (3) and [Fe(III) (salophene)Cl] (4) blocked cellular growth, caused a strong release of Cu/Zn SOD and induced apoptosis. In contrast, the manganese analogs [Mn(II) (salophene)] (5) and [Mn(III) (salophene)OAc] (6) inhibited cell growth, caused the programmed cell death only at higher concentrations and did not provoke release of Cu/Zn SOD in any of the four cell lines. Weaker cell death-promoting effects were observed when the salophene moiety of 3 and 4 was replaced with saldach (complexes 7 and 8), indicating the influence exerted by the ligand structure. In conclusion, Schiff base transition metal complexes induce strong inhibitory effects on human lymphoma and leukemia cells.     

Synthesis,characterization and DNA photocleavage study of a novel dehydroacetic acid based hydrazone Schiff’s base and its metal complexes

A series of some novel colored complexes of Co(II), Ni(II), Cu(II), Mn(II) and Zn(II) with a novel dehydroacetic acid based hydrazone Schiff’s base has been synthesized and evaluated for their DNA photocleavage potential. The ligand utilized in the present investigation was synthesized via a condensation reaction between cyanoacetic acid hydrazide and dehydroacetic acid. Further, the ligand was treated with different metal acetates of first transition series in 1:1 and 1:2 (metal to ligand) ratios, respectively, to obtain metal complexes with different ligand to metal stoichiometry. Ligand as well as all the synthesized metal complexes were characterized on the basis of data obtained from the techniques like ¹H and ¹³C NMR, IR spectroscopy, mass spectrometry, UV visible spectroscopy, elemental analysis and molar conductance. ¹H NMR spectrum of Zn(II) complexes showed the coordination of enolic oxygen atom without deprotonation, but in case of DLCu, the deprotonation of enolic proton was occurred prior to coordination. IR data revealed the participation of a carbonyl oxygen atom of ligand in coordination with metal ions. UV visible data confirmed the square-planar and octahedral geometry of the complexes. Mass spectrum showed the formation of both 1:1 and 1:2 metals to ligand stoichiometry. Most of metal complexes exhibited very good DNA photocleavage activities.     

Schiff base pyrazolone complexes of iron (III): synthesis,characterization, antimicrobial and antioxidant activity

A series of novel Schiff base tetradentate ligands and its iron (III) coordination compounds were synthesized, characterized and evaluated for antibacterial and antioxidant activity. All the synthesized ligands and complexes were characterized by spectroscopic and crystallographic techniques. Electronic spectra, Mössbauer spectra, magnetic moment and conductance study evidence the fact of octahedral arrangement around iron (III). The in vitro antimicrobial Schiff base complexes bear polar and nonpolar properties together; this makes them suitable for permeation to the cells and tissues, it enhances the activity against the bacteria. The antioxidant properties were measured with DPPH (2,2’-diphenyl-2-picrylhydrazyl). These properties were due to the unique feature of ligands such as highest lipophilicity, lowest electron withdrawing power and highest polarisability.     

Antimicrobial,DNA cleavage,and antioxidant properties of new series of metal(II) complexes derived from naphthofuran-2-carbohydrazide Schiff base: synthesis and physico-chemical studies

Metal complexes of the type [NiL₂Cl₂]·H₂O and ML₂Cl₂ [M = Co(II), Cu(II), Cd(II), Zn(II), and Hg(II)] where L = Schiff base, derived from condensation of naphthofuran-2-carbohydrazide and 2-chloro-3-formylquinoline have been synthesized. The chelation of the complexes have been inferred through elemental analyses, IR, electronic mass, ¹H NMR, ESR spectral data, magnetic and thermal studies. The measured low molar conductance values in DMF indicate the complexes to be non-electrolytic in nature. The cyclic voltammetric investigation suggested that, the Cu(II) complex is of single electron transfer quasi-reversible nature. The free ligand and its complexes have been evaluated for their in vitro antibacterial and antifungal activities by minimum inhibitory concentration method. The influence of DNA cleavage on all the complexes was analyzed by agarose gel electrophoresis method. The free ligand with its complexes has been studied for their antioxidant activity by DPPH method. The results of bioassay revealed that, the metal complexes are active than the free ligand and their biological activity increases on complexation.     

A possible correlation between antioxidant and antidiabetic potentials of oxovanadium(IV) complexes

Diabetes mellitus is one of the metabolic disorders resulting from excess production of reactive oxygen species (ROS) over the normal level and also due to dysfunction in the antioxidant defense mechanism, possibly both occurring simultaneously. Excess ROS are normally scavenged by antioxidants. Transition metal complexes exhibit such antioxidant property by scavenging the excess free radicals (one type of ROS) in such disorders. In this study, we report on synthesis, characterization, and in vitro study on antioxidant property of a few new ester-based vanadium(IV) complexes, namely, bis(1,1-dimethylethylpropanedioato)oxovanadium(IV)—[VO(DTBM)₂]; bis(methyl-3-oxopentanoato)oxovanadium(IV)—[VO(MPA)₂]; bis(ethyl-3-oxopentanoato)oxovanadium(IV)—[VO(EPA)₂]; bis(2-methyl-1,3-dimethylpropanedioato)oxovanadium(IV)—[VO(DMMM)₂] and bis(2-bromo-1,3-diethylpropanedioato)oxovanadium(IV)—[VO(BDEM)₂], and also furan-based vanadium complexes. Antidiabetic potential of selected complexes has been estimated. An attempt has also been made to correlate antioxidant and antidiabetic potentials of selected complexes. Our study reveals that compounds exhibiting higher glucose lowering effect seem to possess good antioxidant potential as well.     

Cytotoxic activity of Gd(III)- and Dy(III)-complexes

The complexes of gadolinium(III) and dysprosium(III) were synthesized by reaction of the respective inorganic salts with 3,5-pyrazoledicarboxylic acid in amounts equal to metal to ligand molar ratio of 1 : 2. The structures of the final complexes were determined by means of spectral and elemental analyses. To help further the binding mode elucidation in the new Gd(III)- and Dy(III)-complexes of H(3)pdc, detailed vibrational analysis was performed on the basis of comparison of experimental vibrational spectra of the ligand and its Ln(III)-complexes using data theoretically predicted by us earlier, as well as data from the literature about related compounds. Significant differences in the IR and Raman spectra of the complexes were observed as compared to the spectra of the ligand. The ligand and the complexes were tested for their cytotoxic activities on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma-derived DOHH-2, characterized by a re-expression of the anti-apoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent manner, which enabled the construction of dose-response curves and the calculation of the corresponding IC(50) values. The inorganic salts exerted a very weak cytotoxic effect on these cells. This is in contrast to the lanthanide complexes, which exhibited potent cytotoxic activity, even more than the activity of cisplatin towards K-562 and DOHH-2 cell lines.