Thiosemicarbazone Ligands Research Articles

Chemical and biological studies of Re(I)/Tc(I) thiosemicarbazonate complexes relevant for the design of radiopharmaceuticals

Five thiosemicarbazones (H2Ln) derived from 4,6-diacetylresorcinol (n = 1–4) and salicylaldehyde (n = 5) have been synthesized and spectroscopically characterized. Single crystal X-ray diffraction studies on some of them show that the molecular structure is dominated by intramolecular hydrogen bonds involving the O(1)–H group of the resorcinol/salicylaldehyde group and the azomethinic nitrogen atom and sulfur atom of the thiosemicarbazone arm. All of the ligands react with fac-[ReBr(CO)3(CH3CN)2] in the presence of NEt3 to form the stable anionic complexes [NHEt3][fac-[Re(Ln)(CO)3] (1–5). The thiosemicarbazonate ligand, as suggested by spectroscopic data and confirmed by X-ray diffraction, acts as a tridentate S,N,O system. The complexes are stable in solution for weeks, although other dimeric species were also detected by X-ray diffraction analysis. The reaction of fac-[99mTc(CO)3(H2O)3]+ with the appropriate ligand at 100 °C for 30 min yielded the complexes [fac-[99mTc(Ln)(CO)3]− (Tc1–Tc5). The radiochemical yield and purity were determined by HPLC and their chemical identity was ascertained by comparing their radiochromatogram with the chromatogram of the rhenium congeners (1–5). The results of biodistribution studies in mice on the five technetium compounds showed rapid blood clearance and fast liver uptake that slowly cleared into the intestines, a finding that indicates the hepatobiliary tract as the major excretory pathway. HPLC analysis of urine and blood serum samples from mice injected with the 99mTc complexes confirmed their in vivo stability since the predominant radiochemical species had the same retention time as the corresponding injected compound.

Exploring DNA binding ability of two novel α-N-heterocyclic thiosemicarbazone palladium(II) complexes

One mononuclear and another dinuclear Pd(II) complexes bearing a α-N-heterocyclic thiosemicarbazone ligand have been synthesized, fully characterized and studied as biological agents. In both complexes, the palladium center is coordinated to 3,5-diacetyl-1,2,4-triazol bis(N4,N4-dimethylthiosemicarbazone) via three sites (N, N and S). Their binding ability to DNA has been evaluated using spectroscopic and biophysical techniques. Molecular docking and molecular dynamics calculations supports the existence of a minor groove binding mode between the studied compounds and DNA.

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)2(O2CO)]Cl·6H2O 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)2(O2CO)]Cl·6H2O 2 was used to produce anhydrous [Co(phen)2(H2O)2](NO3)33. Subsequently, anhydrous [Co(phen)2(H2O)2](NO3)33 was reacted with MeATSC 1 to produce [Co(phen)2(MeATSC)](NO3)3·1.5H2O·C2H5OH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV–visible, and multinuclear NMR (1H, 13C, and 59Co) spectroscopy, along with HRMS, and conductivity measurements, where appropriate. Interactions of MeATSC 1 and complex 4 with calf thymus DNA (ctDNA) were investigated by carrying out UV–visible spectrophotometric studies. UV–visible spectrophotometric studies revealed weak interactions between ctDNA and the analytes, MeATSC 1 and complex 4 (Kb = 8.1 × 105 and 1.6 × 104 M−1, respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC50 = 34.4 ± 5.2 μM when compared to IC50 = 13.75 ± 1.08 μM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨm). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨm, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.

Synthesis, characterization and in vitro evaluation of anticancer activity of a new water-soluble thiosemicarbazone ligand and its complexes

A new water-soluble thiosemicarbazone ligand, 4-hydroxyl-3-({[(methylamino)carbonothioyl] hydrazono}methyl)benzoic acid (H3LCOOH) and its complexes with Cu(II), Ni(II), Zn(II), Fe(III) and Mn(III) were synthesized and characterized. These compounds were characterized by conductivity, magnetic susceptibility, elemental analysis, FT-IR, 1H NMR, 13C NMR, and UV–Vis spectroscopy. All the compounds have sufficient solubility and stability in water as a safe, green, and biologic solvent. The compounds were evaluated for their anticancer activities against the human chronic myelogenous K562 leukemia and human breast carcinoma MCF-7 cell lines. All the complexes significantly showed more anticancer activity than the ligand alone and the Cu(II) complex showed considerable cytotoxicity against the tested cell lines. The mechanism of action of the most potent complex, Cu(HLCOO) against K562 cell line was further explored by fluorescence microscopy, flow cytometry, cell cycle and reactive oxygen species (ROS) assays. Hoechst staining and flow cytometry indicated the apoptosis induction ability of Cu(HLCOO) on K562 cells. Mechanistic studies indicated that Cu(HLCOO) complex caused cell cycle arrest at G0/G1 phase and this complex was able to inhibit the cell cycle in a time-dependent manner. Cu(HLCOO) can also increase the reactive oxygen species levels in the K562 cells. The obtained results suggest that the studied compounds can be helpful candidates for further evaluations as chemotherapeutic agents in the treatment of cancer.

Synthesis, and biological evaluation of complexes based on thiosemicarbazone ligand

Abstract Synthesis and evolution of antioxidant and antitumor compounds is a prominent discipline of science. New ligand, 3-(4-hydroxyphenyl)-1-phenyl-1h-pyrazole-4-carbaldehyde 4N-(2-pyridyl)thiosemicarbazone (H2L) and its complexes [Mn2HLCl3(H2O)5]H2O, [CoH2LCl2(H2O)2]H2O, [NiHLCl(H2O)2]H2O, [CuH2LCl2], [ZnHL(CH3COO)(H2O)2]H2O and [CdHL(CH3COO)(H2O)2]H2O were isolated and characterized by diverse spectroscopic studies, electronic absorption spectral studies and magnetic studies. From IR spectra of H2L behaves in a bidentate, tridentate or tetradentate way. DFT calculations showed that the highest occupied molecular orbitals (HOMO) of the complexes are located mainly on the metal and sulphur atoms, whereas the lowest unoccupied molecular orbitals (LUMO) are essentially centered on both the N-heterocyclic core and the largely delocalized thiosemicarbazone backbone. The kinetic and thermodynamic parameters for each stage of decomposition step were calculated from thermal data. It has been found that although H2L proved to exhibit potent antioxidant activity followed by Mn(II), Cd(II), Zn(II) and Ni(II) complexes using ABTS assay. Cobalt complex can be promoted as better antioxidant agent as DPPH radical scavenging activity. Finally, H2L showed the highest cytotoxic activity followed by Mn(II), Ni(II), Cd(II), Zn(II), and Cu(II) complexes.

Synthesis and structure of complexes (NiII, AgI) of substituted benzaldehyde thiosemicarbazones and antitubercular activity of NiII complex

Complexes of 4-chlorobenzaldehyde thosemicarbazone (H1L) with Ni(II), [Ni(1L)2] 1 and Ag(I), [Ag2(μ-X)2(η1-S-H1L)2(PPh3)2] (X = Cl, 2; Br, 3) have been synthesized and characterized by elemental analysis, IR and 1H NMR spectroscopy. Ag(I) complexes, containing the 4-methylbenzaldehyde thiosemicarbazone (H2L) ligand complexes [Ag2(μ-X)2(η1-S-H2L)2(PPh3)2] (X = Cl, 4; Br, 5) have also been synthesized. Complexes 1, 3 and 4 are also characterized by single crystal crystallography to investigate the effect of substituent at phenyl ring of the thiosemicarbazone on the bonding behavior of these Ag(I) complexes. H1L and its Ni(II) complexes were evaluated for their anti-tubercular activities and it was found that the anti-TB actitivy of H1L was enhanced on complexation with Ni(II) for complex 1. Molecular docking of H1L and its nickel complex has also been examined. The results of these studies support the molecular design of the these molecules and have provided a significant background to further examine their antitubercular activity.

Thiosemicarbazonate complexes with affinity for amyloid-β fibers: synthesis, characterization and biological studies.

Aim: Obtain radioimages of amyloid-β fibers using 99mTc-complexes. Methodology: Tridentate thiosemicarbazone and thiocarbonohydrazone ligands containing fragments (stilbene, azobenzene, benzothiazole or benzoxazole) with affinity for amyloid-ß fibers and its Re(I) complexes have been prepared. The molecular structures of several ligands and complexes were determined by x-ray diffraction. Binding affinity studies toward Aß1-42 fibers were performed for the ligands and Re(I) complexes. The ability of formation of some 99mTc(I) complexes, their biodistribution and in vivo stability have been established. Results & conclusion: Complexes of stilbene and benzothiazole thiosemicarbazonates show similar affinity for amyloid-β fibers to the free ligand. These 99mTc complexes present a reasonable in vivo stability and a low capability to cross the blood-brain barrier although not sufficient to brain amyloid imaging.

Effect of Stacking Interactions on the Translation of Structurally Related Bis(thiosemicarbazonato)nickel(II) HER Catalysts to Modified Electrode Surfaces.

A series of crystalline nickel(II) complexes (1-3) based on inexpensive bis(thiosemicarbazone) ligands diacetylbis(4-methyl-3-thiosemicarbazone) (H2ATSM), diacetylbis(4,4-dimethyl-3-thiosemicarbazone) (H2ATSDM), and diacetylbis[4-(2,2,2-trifluoroethyl)-3-thiosemicarbazone] (H2ATSM-F6) were synthesized and characterized by single-crystal X-ray diffraction and NMR, UV-visible, and Fourier transform infrared spectroscopies. Modified electrodes GC-1-GC-3 were prepared with films of 1-3 deposited on glassy carbon and evaluated as potential hydrogen evolution reaction (HER) catalysts. HER studies in 0.5 M aqueous H2SO4 (10 mA cm-2) revealed dramatic shifts in the overpotential from 0.740 to 0.450 V after extended cycling for 1 and 2. The charge-transfer resistances for GC-1-GC-3 were determined to be 270, 160, and 630 Ω, respectively. Characterization of the modified surfaces for GC-1 and GC-2 by scanning electron microscopy and Raman spectroscopy revealed similar crystalline coatings before HER that changed to surface-modified crystallites after conditioning. The surface of GC-3 had an initial glasslike appearance before HER that delaminated after HER. The differences in the surface morphology and the effect of conditioning are correlated with crystal-packing effects. Complexes 1 and 2 pack as columns of interacting complexes in the crystallographic a direction with short interplanar spacings between 3.37 and 3.54 Å. Complex 3 packs as columns of isolated molecules in the crystallographic b direction with long-range interplanar spacings of 9.40 Å.

Group 10 metal complexes with a tetradentate thiosemicarbazonate ligand: Synthesis, crystal structures and computational insights into the catalysis for C–C coupling via Mizoroki-Heck reaction

A series of mononuclear complexes has been synthesized by reactions of group 10 metal ions with bis(4-phenyl-3-thiosemicarbazone) (H2bPht), affording compounds of general formula [MII(bPht)] (M = Ni, Pd and Pt). Their characterization involved FTIR, UV–Vis, 1H NMR, CV, DPV and elemental analysis. Furthermore, the crystal structures of all complexes have been determined, showing that the thiosemicarbazonate ligand is coordinated as a tetradentate N,N,S,S-donor forming three five-membered chelate rings. The catalytic activity of [MII(bPht)] in Heck's C–C coupling reaction using styrene and iodobenzene to obtain stilbenes has been evaluated. It was verified that the NiII and PtII complexes present low catalytic activity, while the PdII complex showed a conversion of 99% within 24 h. Trans-stilbene was identified as the major product of the coupling reaction, up to 90%. DFT studies were also performed in order to better understand the catalytic behavior of these complexes giving support for a new route for Mizoroki-Heck reaction.

Synthesis, Structural Characterization, Molecular Modeling and DNA Binding Ability of CoII, NiII, CuII, ZnII, PdII and CdII Complexes of Benzocycloheptenone Thiosemicarbazone Ligand.

Six novel complexes of transition metal namely, [CoLCl2(H2O)2]0.5H2O, [NiLCl2(H2O)2]0.5H2O, [CuLCl2]0.5H2O, [ZnLCl2], [PdLCl2]H2O and [CdLCl2]H2O, where L is benzocycloheptenone thiosemicarbazone ligand, have been obtained. The confirmation of the structures of the obtained metal chelates depends on the different spectral and physicochemical techniques including CHN analysis, infrared spectra, molar conductivity measurement, UV-vis, thermogravimetric analysis and magnetic moment. The infrared spectral results ascertained that the ligand behaved as neutral bidentate connecting the metal centers via N and S atoms of C=N and C=S groups, respectively. The UV-Vis, molar conductivity and magnetic susceptibility results implied that the geometrical structures of the metal chelates are octahedral for Co(II) & Ni(II) complexes, tetrahedral for Zn(II) & Cd(II) complexes and square planar for Cu(II) & Pd(II) complexes which have been confirmed by molecular modeling studies. Moreover, the mode of interaction between some chosen metal complexes towards SSDNA has been thoughtful by UV-Vis spectra and viscosity measurements. The value of the intrinsic binding constant (Kb) for the examined compounds has been found to be lower than the binding affinity of the classical intercalator ethedium bromide. Also, the viscosity measurements of the complexes proved that they bind to DNA, most likely, by a non-intercalative mode like H-bonding or electrostatic interactions.

Synthesis, Characterization, and in Vitro Anticancer Activity of Copper and Zinc Bis(Thiosemicarbazone) Complexes.

A series of eight bis(thiosemicarbazone) ligands and 16 of their respective copper(II) and zinc(II) complexes containing a combination of hydrogen, methyl, pyridyl, phenyl, and/or ethyl substituents at the diimine position of the ligand backbone were synthesized and characterized. The objective of this study was to identify the structure-activity relationships within a series of analogues with different substituents at the diimine position of the backbone and at the terminal N atom. The Cu(II) complexes Cu(GTSM2), Cu(GTSCM), Cu(PyTSM2), Cu(EMTSM2) and Cu(PGTSM2) demonstrated a distorted square planar geometry, while the Zn(II) complexes Zn(ATSM2)(DMSO), Zn(PyTSM2)(DMSO), and Zn(PGTSM2)(H2O) formed a distorted square pyramidal geometry. Cyclic voltammetry showed that the Cu(II) complexes display quasi-reversible electrochemistry. Of the agents, Cu(II) glyoxal bis(4,4-dimethyl-3-thiosemicarbazone) [Cu(GTSM2)] and Cu(II) diacetyl bis(4,4-dimethyl-3-thiosemicarbazone) [Cu(ATSM2)] demonstrated the greatest antiproliferative activity against tumor cells. Substitutions at the diimine position and at the terminal N atom with hydrophobic moieties markedly decreased their antiproliferative activity. Complexation of the bis(thiosemicarbazones) with Zn(II) generally decreased their antiproliferative activity, suggesting the Zn(II) complex did not act as a chaperone to deliver the ligand intracellularly, in contrast to similar bis(thiosemicarbazone) cobalt(III) complexes [King et al. Inorg. Chem. 2017, 56, 6609-6623]. However, five of the eight bis(thiosemicarbazone) Cu(II) complexes maintained or increased their antiproliferative activity, relative to the ligand alone, and a mechanism of Cu-induced oxidative stress is suggested. Surprisingly, relative to normoxic growth conditions, hypoxia that is found in the tumor microenvironment decreased the antiproliferative efficacy of most bis(thiosemicarbazones) and their copper complexes. This was independent of the potential hypoxia-selectivity mediated by Cu(II/I) redox potentials. These results provide structure-activity relationships useful for the rational design of bis(thiosemicarbazone) anticancer agents.

New series of water-soluble thiosemicarbazones and their copper(II) complexes as potentially promising anticancer compounds

New water soluble thiosemicarbazone ligands, namely 3-(3-{[(aminocarbonothioyl) hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L1Cl), 3-[4-hydroxy-3-({[(methylamino)carbonothioyl]hydrazono}methyl)benzyl]-1-methyl-1H-imidazol-3-ium chloride (H2L2Cl) and 3-(3-{[(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L3Cl) were synthesized through 1:1 condensation reaction of thiosemicarbazide derivatives with 3-(3-formyl-4-hydroxybenzyl)-1-methyl-1H-imidazole-3-ium chloride (SalimiCl) and characterized by elemental analysis and spectroscopic methods (UV–Vis, 1H NMR, FTIR). Single crystals of H2L1Cl and H2L2Cl were prepared for crystallographic analysis, which showed similar X-ray structures for both ligands with chiral P212121 space group. The ligands were used for synthesis of the following copper(II) complexes: [Cu(HL1)Cl]Cl, [Cu(HL2)Cl]Cl·H2O, and [Cu(HL3)Cl]Cl. All complexes were characterized by physico-chemical and spectroscopic methods. The X-ray structure of [Cu(HL1)Cl]Cl was orthorhombic with Pcba space group while [Cu(HL2)Cl]Cl·H2O was triclinic with Pī space group. Both complexes were mononuclear, with tridentate ligands in a thione form. All of the studied compounds showed good solubility and stability in water. The measurement of the molar conductance showed the release of Cl− into solution and substitution of water instead of the coordinated chloride. Among the studied complexes, only [Cu(HL3)Cl]Cl shows a quasi-reversible redox behavior with its reduction and oxidation peak potentials separated by a value of about 0.120V (Epc=−0.310V and Epa=−0.190V) indicating one-step and one-electron transfer for CuII/CuI redox couple. The cytotoxic effect of the compounds was measured using the MTT assay on MCF-7 and K562 cell lines and the results showed that [Cu(HL3)Cl]Cl and H2L3Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the MCF-7 cells showed the apoptosis cell death after treating with the H2L3Cl and [Cu(HL3)Cl]Cl. Also studies of cell cycles confirmed the cell cycle arrest in G2 phase for H2L3Cl and [Cu(HL3)Cl]Cl.

Preparation and Crystal Structure Determination of Zinc (II) Bromide Complexes at the Presence of Various Ligands

In this paper, we report the syntheses and crystal structuredetermination of three mononuclear and four-coordinated zinc(II) bromide complexes with chemical formula of [Zn(tsc)2]Br2 (1), Zn(PPh3)2Br2 (2) and Zn(Brcatsc)Br2 (3). The synthesized complexes are characterized by elemental analysis (CHN) and theircrystal structures are investigated by single crystal X-ray diffraction. In complex 1, the TSC coordinates to the zinc(II) ion as a bidentate ligand via N and S atoms. In complex 3, the thiosemicarbazone ligand Brcatsc coordinates to zinc(II) ion as a monodentate ligand via S atom. In these complexes, the zinc(II) ion coordinated in a distorted tetrahedral coordination geometry.

Crystal packing of a zinc(II)-azide complex with a N,N,S-tridentate thiosemicarbazone ligand: An experimental and computational study

The aim of this study was to provide a crystallographic and electronic analysis of a zinc(II)-azide complex with a N,N,S-tridentate thiosemicarbazone ligand. The characterization was performed by single-crystal X-ray diffraction, elemental analysis and FT-IR spectroscopy. This compound showed a distorted square-planar structure and its crystal structure was in the triclinic space group P1¯ with Z = 2. Based on the Hirshfeld surface analysis, the van der Waals forces, N⋅⋅⋅H hydrogen bonds and C–H⋅⋅⋅π are the main intermolecular interactions that stabilize the crystal packing assembly. In addition, the Density Functional Theory (DFT) was used to predict the electronic properties. DFT calculations estimated interaction energy of −12.6 kcal mol−1 required to form the dimer structure. Nevertheless, based on a Natural Bond Orbital (NBO) analysis, two hydrogen bonds between nitrogen atoms of the azide group and the hydrogen atom of the amine one (N–H⋅⋅⋅N) are the main interactions responsible for the stabilization of the dimer structure studied. In addition, we were also able to characterize other important intermolecular interactions as the Sulfur⋅⋅⋅Sulfur and the C–H⋅⋅⋅N formed between the azide groups and the aromatic rings performed with the Quantum Theory of Atoms in Molecules (QTAIM).

Nickel Complexes Bearing SNN and SS Donor Atom Ligands: Synthesis, Structural Characterization and Biological activity

Based on a tridentate thiosemicarbazone ligand {HL = 4‐(2,4‐dimethylphenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide}, the nickel complexes [NiCl(L)] 1, [Ni(L)(diEtdtc)(H2O)] 2 and [Ni(L)(pipdtc)(H2O)] 3 were prepared {NadiEtdtc = sodium diethyldithiocarbamate and Napipdtc = sodium piperidine dithiocarbamate} and their structures were elucidated according to their elemental analyses, solution conductivities, magnetic moments and spectroscopic (IR and electronic) data. X‐ray single crystal studies have confirmed the structure of 1 as a square planar complex in which each nickel atom is linked to three (two nitrogen and one sulfur) atoms from the thiosemicarbazone ligand and a chlorine atom to ensure the complex neutrality. Moreover, the asymmetric unit cell of the complex was found to consist of two independent complex molecules of slightly different conformations (A&B). The complexes, especially the binary one, displayed high bactericidal activities that, in several instances, were comparable to or higher than those of the chloramphenicol standard.

Cu(II) and Ni(II) Complexes with New Tridentate NNS Thiosemicarbazones: Synthesis, Characterisation, DNA Interaction, and Antibacterial Activity.

This paper reports the synthesis and detailed characterisation of copper(II) and nickel(II) complexes with tridentate thiosemicarbazone ligands H 2 L1 and H 2 L2 derived from 2-acetylpyrazine. The ligands and their metal complexes were characterised by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR, and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The crystal structure of the H 2 L1 ligand was determined by single crystal X-ray diffraction studies. The spectral data showed that the thiosemicarbazone behaves as an NNS tridentate ligand through the nitrogen atoms of the azomethine group and pyrazine ring and the sulphur atom of the thioamide group. Elemental and thermal analyses indicated that the obtained metal complexes had a 1 : 1 stoichiometry (metal-ligand). The interactions between these complexes and calf thymus DNA (CT-DNA) were studied by electronic absorption and viscosity measurements. The activities of these compounds against oxidative DNA cleavage were examined by agarose gel electrophoresis. Cu(II) and Ni(II) complexes can wind DNA strands through groove interactions and promote strand breakage of the plasmid pmCherry under oxidative stress conditions. Moreover, all the complexes could interact more strongly with DNA than could with the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains (S. aureus ATCC 25923, L. monocytogenes ATCC 19115, and B. cereus ATCC 10876) and Gram-negative bacterial strains (E. coli ATCC 25922, S. typhimurium ATCC 14028, and K. pneumoniae ATCC BAA-2146) using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

Anticancer and biological properties of a Zn-2,6-diacetylpyridine bis(thiosemicarbazone) complex

Herein, to develop a multi-target anticancer metal agent and achieve a "1 + 1 > 2" pharmaceutical effect, we rationally designed and synthesized five complexes (C1-C5) by synergistically exploiting the properties of Zn(ii) and a series of modified 2,6-diacetylpyridine bis(thiosemicarbazone) ligands. By investigating the structure-activity relationships, we found that the binuclear Zn(ii) complex (C5) acts against human bladder cancer cells (T-24) with significant cytotoxicity. We subsequently determined the multiple anticancer mechanisms of C5 to T-24 cells, including inhibiting the activity of topoisomerase I (Topo I), blocking the cell cycle in the S phase, and inducing apoptosis and autophagy in T-24 cells. Furthermore, C5 inhibited the migration of T-24 cells and showed a significant cytostatic effect in the T-24 3D spheroid model.

Biological evaluation of copper(II) complexes on N(4)−substituted thiosemicarbazide derivatives and diimine co-ligands using DNA interaction, antibacterial and in vitro cytotoxicity

A number of alternatives were made to overcome numerous life-threatening infectious diseases by metal-based anticancer compounds. At present, thiosemicarbazones and their metal complexes have received significant consideration as a result of their metal DNA-interaction, structural diversity and availability of bonding modes. In this study, the coordination characteristics of nine diimine copper(II) complexes with sulfur containing ligands, [Cu(L)2] (1–3), [Cu(L)(bpy)]Cl (4–6) and [Cu(L)(phen)]Cl (7–9) (L = H(L1)–H(L3), phen = 1,10-phenanthroline, bpy = 2,2′-bipyridyl, H(L1) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-methylhydrazinecarbothioamide, H(L2) = (Z)-N-ethyl-2-((4-methoxynaphthalen-1-yl)methylene)hydrazinecarbothioamide and H(L3) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-phenylhydrazinecarbothioamide] have been synthesized from 4-methoxy-1-naphthaldehyde along with N(4)-substituted thiosemicarbazide derivatives. The synthesized ligands and their Cu(II) complexes were characterized through different spectroscopic techniques and square-planar coordination was proposed. Biological evaluation such as DNA-cleavage, antibacterial and in vitro cytotoxicity of thiosemicarbazone ligands and their resultant Cu(II) complexes were analyzed. Interestingly, Cu(II) complex containing heteroaromatic moiety 9 had potential cytotoxic activity with strong DNA-interaction. In the future, these may be helpful to design more effective novel chemotherapeutic drugs.

Synthesis, Characterization and the Antibacterial Activity of a New Ni(II) Complex of Thiosemicarbazone Ligand.

Novel complex of Ni(II) of ligand 2-(anilinoacetyl)-N-(3-methylphenyl)hydrazine-1- carbothioamide (H2L) has been synthesized and characterized by 1HNMR, IR, elemental analyses, molar conductance, UV-visible spectra, magnetic susceptibility measurements ,thermogravimetric analysis (TGA/DTG) and X-ray differaction pattern. The result confirmed that the ligand behaved as neutral bidentate, coordination take place via carbonyl oxygen(C=O) and N(2)H groups. Nickel complex is more thermally stable than free ligand . Nickel(II) complex is mononuclear, adopt square planar geometry . The ligand and complex have been tested for their inhibitory effect on the growth of bacteria against gram-positive (Streptococcus pyogenes) and gram-negative (Escherichia coli). The result revealed that Ni(II) complex showed a higher antibacterial activity against gram positive (Streptococcus pyogenes) and gram negative (Escherichia coli) bacteria than the ligand.

The BIOLOGICAL EFFICACY OF MIXED LIGAND COPPER(II) COMPLEXES OF N(4)-SUBSTITUTED THIOSEMICARBAZONE AND DIIMINE CO-LIGANDS AS CHELATING N, N’- DONOR LIGAND

Objective: In modern years, the biggest dare is to develop new chemotherapeutic agents with high efficiency as well as low toxicity. Hence, to defeat this challenge, extensive endeavors were taken on thiosemicarbazone based metal complexes.
 Methods: A sequence of nine thiosemicarbazone based diimine copper(II) complexes derived from three sulfur-containing ligands N-methyl-2- ((1-methyl-1H-pyrrol-2-yl)methylene)hydrazinecarbothioamide H(L1), N-ethyl-2-((1-methyl-1H-pyrrol-2-yl)methylene)hydrazinecarbothioamide H(L2), and N-benzyl-2-((1-methyl-1H-pyrrol-2-yl)methylene)hydrazinecarbothioamide H(L3). The molecular structures and coordination possibilities of thiosemicarbazone ligands toward the central metal ions have been validated by analytical and spectral techniques such as molar conductance, elemental analysis, ultraviolet–Vis, Fourier-transform infrared, and electron paramagnetic resonance spectroscopy confirms that the thiosemicarbazones ligands are coordinated to copper through NS’ donor and NN’ donor of diimine. The antimicrobial activity and DNA cleavage effectiveness of thiosemicarbazone derivatives and copper(II) complexes were assessed by disc diffusion and agarose gel electrophoresis methods.
 Results: All the spectral studies authenticated that the square planar geometry of the thiosemicarbazone copper(II) complexes 1–9. From the results of antibacterial activity against selected Gram-positive (Bacillus thuringiensis) and Gram-negative (Escherichia coli) bacterial strains, complex 8 exhibited noteworthy activity. Interestingly, copper(II) complexes bearing 1,10-phenanthroline (phen) moiety displayed outstanding results together with N(4)-substituted thiosemicarbazone derivatives and causes complete DNA degradation of SC (supercoiled) pUC18 DNA.
 Conclusion: A variety of substitutions at the thioamide nitrogen atoms have shown potential biological activity. Henceforth, N(4)-substituted thiosemicarbazone based copper(II) complexes virtually reach the effectiveness of conventional chemotherapeutic drugs.