New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. synthesis,spectral studies and in vitro anti-amoebic activity

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole.     

Synthesis, characterization and in vitro anti-amoebic activity of new palladium(II) complexes with 5-nitrothiophene-2-carboxaldehyde N(4)-substituted thiosemicarbazones

Reaction between [Pd(DMSO)(2)Cl(2)] (DMSO=dimethylsulfoxide) and N(4)-substituted thiosemicarbazones derived from 5-nitrothiophene-2-carboxaldehyde (L) afforded the complexes [Pd(L)Cl(2)]. These new complexes have been characterized by elemental analyses and spectroscopic studies. Spectroscopic studies reveal that thionic sulfur and azomethine nitrogen atom of thiosemicarbazones are coordinated to metal ion. The testing of the anti-amoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 9, 10, and 11 might be endowed with important anti-amoebic properties since they showed less IC(50) values than metronidazole. Moreover, compound 11 displays notable amoebicidal activity than metronidazole (IC(50) values of 0.79 microM vs 1.93 microM, respectively).     

Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives

Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.     

Synthesis,characterization and DNA binding and cleavage properties of ruthenium(II) complexes with various polypyridyls

Polypyridyl chlororuthenium(II) complexes have been synthesized and characterized. The binding mode of the complexes to DNA has been evaluated from the combined results of electronic absorption spectroscopy and viscosity measurement study. The results suggest that complexes 1, 2 and 3 bind to DNA via classical intercalation, electrostatic interaction and partial intercalation mode, respectively. Complex 2 shows less affinity for DNA. Cleavage of pUC19 DNA by complexes has been checked using gel electrophoresis. The data disclose that complex 1 has the highest cleaving ability.     

Synthesis, characterisation and antiamoebic activity of new thiophene-2-carboxaldehyde thiosemicarbazone derivatives and their cyclooctadiene Ru(II) complexes

Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where TSC=thiosemicarbazone). All the compounds have been characterised by elemental analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is concluded that the thionic sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK-9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the thiosemicarbazones.     

Proapoptotic activity in vitro of two novel ruthenium(II) complexes with flavanone-based ligands that overcome cisplatin resistance in human bladder carcinoma cells

In this study we examined their proapoptotic activity of cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(II)3H₂O (1) and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(II)2H₂O (2) towards human bladder carcinoma cell line EJ and its cisplatin resistant subline EJcisR. On the basis of the experiments we carried out, it may be concluded, that: CDDP (cis-diamminedichloridoplatinum) resistance of EJcisR cells is probably based on partial loss of apoptotic pathway activating caspase-8 and increased resistance to DNA strand breaks and/or alkali-labile sites. Increased glutathione levels, as well as activity of P-gp transporter seems to be not relevant in this case. The proapoptotic activity of the ruthenium compounds is higher than that of cisplatin. Higher proapoptotic activity of 1 and 2 when compared to CDDP may be due to the presence of large, lipophilic flavanone-based ligands that may facilitate their trans-membrane transport and their redox activity. 1 and 2 induce apoptosis apparently in more than one way. Although caspase-8 activation and DNA strand breaks and/or alkali-labile sites are caused by the compounds, their ability to cause the oxidative stress in the cells may also participate in apoptosis induction.     

Diastereoisomerically pure pyrazole-3,5-dicarboxylate-bridged dinuclear ruthenium(II) and osmium(II) complexes of 2,2-bipyridine: structural, electrochemical and spectral studies

Pyrazole-3,5-dicarboxylate-bridged dinuclear ruthenium(II) and osmium(II) complexes of 2,2^′-bipyridine of composition [(bpy)₂Ru(pzdc)Ru(bpy)₂](ClO₄) · H₂O (1) and [(bpy)₂Os(pzdc)Os(bpy)₂](ClO₄) · H₂O (2) have been obtained in high yield and have been separated to their homochiral (ΛΛ/ΔΔ) rac (1a, 2a) and heterochiral (ΛΔ/ΔΛ) meso (1b, 2b) diastereoisomers. The distinctive structural features of these diastereoisomers have been characterized by 1-D and 2-D ¹H NMR spectroscopy. The X-ray crystal structure of rac-[(bpy)₂Os(pzdc)Os(bpy)₂](ClO₄) · H₂O (2a) has been determined. The electrochemical and electronic spectral studies have established that there remain difference in properties and hence difference in intermetallic communication between the diastereoisomeric forms in each case.     

Synthesis, characterization and antitumor activity of polymeric copper(II) complexes with thiosemicarbazones of 3-methyl-5-oxo-1-phenyl-3-pyrazolin-4-carboxaldehyde and 5-oxo-3-phenyl-3-pyrazolin-4-carboxaldehyde

New polymeric copper(II) complexes with two tridentate ONS thiosemicarbazone ligands containing substituted pyrazolone moiety were synthesized and characterized by means of spectroscopic, electrochemical and crystallographic techniques. While both ligands exist as different tautomers in the solid state and DMSO-d₆ solution, Cu(II) ion coordinates the ligands from the same tautomeric form with square-pyramidal geometry around each Cu atom. In the crystal structures, the copper(II) complex cation forms polymeric chains {[Cu(L)Cl]⁺}_n with a bridging chlorine atom. One of the complexes was found to have a significantly higher cytotoxic potential in comparison with cisplatin in inhibition of several cell lines (HL60, REH, C6, L929 and B16). The results obtained on the basis of flow cytometry indicated that apoptosis could be possible mechanism of cell death.     

Synthesis and characterization of new ruthenium(II) complexes containing coupled di(2-pyridyl) and 1,3-dithiole units

Two new ruthenium (II) complexes containing coupled di(2-pyridyl) and 1,3-dithiole units, cis-[Ru(Medpydt)₂(NCS)₂] (2, Medpydt = dimethyl 2-(di(2-pyridyl)methylene)-1,3-dithiole-4,5-dicarboxylate) and cis-[Ru(H₂dpydt)₂(NCS)₂] (3, H₂dpydt = 2-(di(2-pyridyl)methylene)-1,3-dithiole-4,5-dicarboxylate), have been synthesized and characterized. The structure of complex 2 has been determined by X-ray crystallography. There exist intermolecular H-bonding interactions between carbomethoxy groups on neighboring pyridine rings giving rise to 2D H-bonded arrays. The metal-to-ligand charge-transfer (MLCT) absorptions were observed around 480 nm. Redox properties of ruthenium complexes have been investigated by cyclic voltammetry. Solar cells involving thin films of anatase TiO₂ impregnated with cis-[Ru(H₂dpydt)₂(NCS)₂] were prepared, and the photovoltaic performance was preliminarily investigated.     

Selective recognition of homocysteine and cysteine based on new ruthenium(II) complexes

A series of the new ruthenium(II) complexes with different number of aldehyde groups have been synthesized and characterized for the simple and selective sensing of homocysteine (Hcy) and cysteine (Cys). The reaction of these ruthenium(II) complexes with Hcy and Cys afforded thiazinane or thiazolidine derivatives which resulted in the obvious changes in the UV-visible spectra and strong enhancement of the luminescence intensity of the system. The luminescence enhancement of [Ru(dmb)₂(L2)]²⁺ (dmb: 4,4′-dimethyl-2,2′-bipyridine) showed a good linearity in the concentration of 4.2-350 μM and 6-385 μM with the detection limits of 0.3 μM and 1 μM for Hcy and Cys, respectively. The absorption and emission bands from metal-to-ligand charge transfer transition in the visible region and the large Stokes shift of the ruthenium(II) complex chromophore made it suitable for biological applications.     

Antibacterial,antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones

1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone 4‐ethyl‐thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C₂H₅OH·( 1 ), [Cu(L)₂]·H₂O ( 2 ), [Cu(L)(Br)]·H₂O·CH₃OH ( 3 ), [Cu(L)(NO₃)]·2C₂H₅OH ( 4 ), [VO₂(L)]·2H₂O ( 5 ), [Ni(L)₂]·H₂O ( 6 ), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, ¹H NMR and ¹³C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico‐chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) ( 2 , 4 ), and vanadium(V) ( 5 ) complexes have been determined by single‐crystal X‐ray diffraction. The composition of the coordination polyhedron of the central atom in 2 , 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4 , it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL‐60 cells was tested.     

Synthesis,characterization, redox behavior,DNA and protein binding and antibacterial activity studies of ruthenium(II) complexes of bidentate schiff bases

Two new ruthenium(II) complexes of Schiff base ligands (L) derived from cinnamaldehyde and ethylenediamine formulated as [Ru(L)(bpy)₂](ClO₄)₂, where L¹ = N,N’-bis(4-nitrocinnamald-ehyde)ethylenediamine and L² = N,N’-bis(2-nitrocinnamaldehyde)-ethylenediamine for complex 1 and 2, respectively, were isolated in pure form. The complexes were characterized by physicochemical and spectroscopic methods. The electrochemical behavior of the complexes showed the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of the complexes with calf thymus DNA (CT-DNA) using absorption, emission spectral studies and electrochemical techniques have been used to determine the binding constant, K_b and the linear Stern–Volmer quenching constant, K_SV. The results indicate that the ruthenium(II) complexes interact with CT-DNA strongly in a groove binding mode. The interactions of bovine serum albumin (BSA) with the complexes were also investigated with the help of absorption and fluorescence spectroscopy tools. Absorption spectroscopy proved the formation of a ground state BSA-[Ru(L)(bpy)₂](ClO₄)₂ complex. The antibacterial study showed that the Ru(II) complexes (1 and 2) have better activity than the standard antibiotics but weak activity than the ligands.     

Synthesis,spectral studies and screening for amoebicidal activity of new palladium(II) complexes derived from thiophene-2-carboxaldehyde thiosemicarbazones

In view of the antiamoebic properties observed for many thiophene-2-carboxaldehyde thiosemicarbazones, a series of N(4)-substituted thiosemicarbazones metal complexes derived from thiophene-2-carboxaldehyde was prepared for evaluation against Entamoeba histolytica. Reaction of thiophene-2-carboxaldehyde with cycloalkylaminothiocarbonylhydrazines having different amines gave the corresponding thiosemicarbazones. Reaction of latter with [Pd(DMSO)(2)Cl(2)] gave requisite palladium thiosemicarbazone complexes of the type [Pd(TSC)Cl(2)] (where TSC=thiosemicarbazones). Screening of antiamoebic activity of these compounds was assayed in vitro against (HM-1:1MSS) strain of E. histolytica. Enhancement of antiamoebic resulted from introducing palladium metal in the thiosemicarbazone moiety. Among the studied compounds, [Pd(2-TCA-1,2,3,4-THQTSC)Cl(2)] (2a) showed better activity.     

Synthesis and in vitro evaluation of palladium(II) salicylaldiminato thiosemicarbazone complexes against Trichomonas vaginalis

Eight mononuclear Pd(II) complexes containing salicylaldiminato thiosemicarbazones (saltsc-R; where R = H (1), 3-OMe (2), 3-^tBu (3) and 5-Cl (4)) as dinegative tridentate ligands were prepared by the reaction of the corresponding thiosemicarbazone with the precursor Pd(L)₂Cl₂ (L = phosphatriazaadamantane or 4-picoline) in the presence of a weak base. These complexes (9-16) were characterised by a range of spectroscopic and analytical techniques including NMR spectroscopy and X-ray diffraction. These complexes along with four other Pd(II) analogues (5-8) were screened for activity in vitro against the Trichomonas vaginalis parasite. Preliminary results show that the type of ancillary ligand as well as the substituents on the aromatic ring of the salicylaldiminato thiosemicarbazone ligand influences the antiparasitic activity of these complexes.     

Targeting topoisomerase II with the chiral DNA-intercalating ruthenium(II) polypyridyl complexes

Many antitumor drugs act as topoisomerase inhibitors, and the inhibitions are usually related to DNA binding. Here we designed and synthesized DNA-intercalating Ru(II) polypyridyl complexes Δ--[Ru(bpy)₂(uip)]²⁺ and Λ-[Ru(bpy)₂(uip)]²⁺ (bpy is 2,2′-bipyridyl, uip is 2-(5-uracil)-1H-imidazo[4,5-f][1,10]phenanthroline). The DNA binding, photocleavage, topoisomerase inhibition, and cytotoxicity of the complexes were studied. As we expected, the synthesized Ru(II) complexes can intercalate into DNA base pairs and cleave the pBR322 DNA with high activity upon irradiation. The mechanism studies reveal that singlet oxygen (¹O₂) and superoxide anion radical (O₂^•−) may play an important role in the photocleavage. The inhibition of topoisomerases I and II by the Ru(II) complexes has been studied. The results suggest that both complexes are efficient inhibitors towards topoisomerase II by interference with the DNA religation and direct topoisomerase II binding. Both complexes show antitumor activity towards HELA, hepG2, BEL-7402, and CNE-1 tumor cells. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Complexes [Au(H2Ac4DH)Cl]?MeOH (1) [Au(H₂2Ac4Me)Cl]Cl (2) [Au(H₂2Ac4Ph)Cl]Cl?2H₂O (3) and [Au(H₂2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.     

Synthesis and in vitro antitumoral activity of novel O,O'-di-2-alkyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate ligands and corresponding platinum(II/IV) complexes

Syntheses of two novel ligand precursors O,O'-diisopropyl- (1a) and O,O'-diisobutyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate dihydrochloride monohydrate (1b) and the corresponding dichloroplatinum(II) (2a and 2b) and tetrachloroplatinum(IV) complexes (3a and 3b) are described here. The substances were characterized by IR, (1)H and (13)C spectroscopy and elemental analysis. Crystal structures were determined for 1a and the corresponding platinum(IV) complex, 3a. In vitro antiproliferative activity was determined against tumor cell lines: human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear PBMC cells) using KBR test (Kenacid Blue Dye binding test). The IC(50)(microM) values for the most active compound 3a were: 30.48+/-2.54; 12.26+/-2.60; 13.68+/-3.22; 80.18+/-24.07 and 71.30+/-21.70, respectively.     

Synthesis and structural studies of gallium(III) and indium(III) complexes of 2-acetylpyridine thiosemicarbazones

Four 2-acetylpyridine ⁴N-alkyl thiosemicarbazones, and their Ga(III) and In(III) complexes have been prepared and characterised by fluorescence, UV-Vis, IR, ¹H and ¹³C NMR spectroscopy, mass spectrometry and X-ray crystallographic analysis. Comparison of the crystal structures gave an insight into the nature of the complexes formed, demonstrating a preference for [ML₂]⁺ type complexes with gallium and [MLX₃] species with indium. Stability studies on two candidates indicated that complex [InL³Cl₂MeOH] was stable to chemical degradation for prolonged periods in human serum, giving this complex potential for further biological evaluation.     

Synthesis, characterization and antibacterial activity of new sulfonamide derivatives and their nickel(II), cobalt(II) complexes

Methanesulfonicacid hydrazide (a sulfonamide compound, msh: CH₃SO₂NHNH₂) derivatives: methylsalicylaldehydemethanesulfonylhydrazone (5msalmsh), 5-methyl-2-hydroxyaceto-phenonemethanesulfonylhydrazone (5mafmsh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these sulfonamide compounds has been investigated by using elemental analyses; FT-IR, ¹H NMR, ¹³C NMR, LC-MS, and UV-Vis spectrometric methods; magnetic susceptibility; conductivity measurements; thermal studies. The crystal structure of 5msalmsh has been investigated by X-ray analysis. The antibacterial activities of synthesized compounds were studied against gram positive bacteria: Staphylococcus aureus, Bacillus subtilis, and Bacillus magaterium; and gram negative bacteria: Salmonella enteritidis, and Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria.     

Nickel(II) and copper(II) complexes of Schiff base ligands containing N4O2 and N4S2 donors with pyrrole terminal binding groups: Synthesis, characterization, X-ray structures, DFT and electrochemical studies

A series of hexadentate ligands, H₂L^m (m = 1−4), [1H-pyrrol-2-ylmethylene]{2-[2-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)ethoxy]phenyl}amine (H₂L¹), [1H-pyrrol-2-ylmethylene]{2-[4-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)butoxy]phenyl}amine (H₂L²), [1H-pyrrol-2-ylmethylene][2-({2-[(2-{[1H-pyrrol-2-ylmethylene]amino}phenyl)thio]ethyl}thio)phenyl]amine (H₂L³) and [1H-pyrrol-2-ylmethylene][2-({4-[(2-{[1H-pyrrol-2-lmethylene]amino}phenyl)thio]butyl}thio) phenyl]amine (H₂L⁴) were prepared by condensation reaction of pyrrol-2-carboxaldehyde with {2-[2-(2-aminophenoxy)ethoxy]phenyl}amine, {2-[4-(2-aminophenoxy)butoxy]phenyl}amine, [2-({2-[(2-aminophenyl)thio]ethyl}thio)phenyl]amine and [2-({4-[(2-aminophenyl)thio]butyl}thio)phenyl]amine respectively. Reaction of these ligands with nickel(II) and copper(II) acetate gave complexes of the form ML^m (m = 1−4), and the synthesized ligands and their complexes have been characterized by a variety of physico-chemical techniques. The solid and solution states investigations show that the complexes are neutral. The molecular structures of NiL³ and CuL², which have been determined by single crystal X-ray diffraction, indicate that the NiL³ complex has a distorted octahedral coordination environment around the metal while the CuL² complex has a seesaw coordination geometry. DFT calculations were used to analyse the electronic structure and simulation of the electronic absorption spectrum of the CuL² complex using TDDFT gives results that are consistent with the measured spectroscopic behavior of the complex. Cyclic voltammetry indicates that all copper complexes are electrochemically inactive but the nickel complexes with softer thioethers are more easily oxidized than their oxygen analogs.