synthesis, characterization and in vitro antiamoebic activity of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones and their Palladium (II) and Ruthenium (II) complexes

Synthesis of new Palladium(II) and Ruthenium(II) complexes of the type, [Pd(L)Cl(2)] and [Ru(eta(4)-C(8)H(12))(L)Cl(2)] [where, L = thiosemicarbazones derived from 5-nitrothiophene-2-carboxaldehyde and cycloalkylaminothiocarbonyl hydrazines] have been isolated by the reaction of [Pd(DMSO)(2)Cl(2)] and [Ru(eta(4)-C(8)H(12))(CH(3)CN)(2)Cl(2)] with 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. The spectral data revealed that the thiosemicarbazones act as bidentate ligands, making use of thionic sulphur and the azomethine nitrogen atom for coordination to the central metal ion. Microdilution method was used for the assessment of antiamoebic activity of all the compounds against HK-9 strain of Entamoeba histolytica. Among all the thiosemicarbazones, 5-NT-4-BPTSCN (3) showed significant antiamoebic activity (IC(50) - 2.56 microM). Enhancement of antiamoebic activity resulted by introducing palladium and ruthenium metals in the thiosemicarbazone moiety. All the Pd(II) and Ru(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones were found more active then their respective ligands. The complexes 1a-4a, 1b and 3b showed antiamoebic activity.     

Pyridine-derived thiosemicarbazones and their tin(IV) complexes with antifungal activity against Candida spp

[(n-Bu)Sn(2Ac4oClPh)Cl₂] (1), [(n-Bu)Sn(2Ac4oFPh)Cl₂] (2), [(n-Bu)Sn(2Ac4oNO₂Ph)Cl₂] (3), [(n-Bu)Sn(2Bz4oClPh)Cl₂] (4), [(n-Bu)Sn(2Bz4oFPh)Cl₂] (5) and [(n-Bu)Sn(2Bz4oNO₂Ph)Cl₂] (6) were obtained by reacting [(n-Bu)SnCl₃] with 2-acetylpyridine-N(4)-orthochlorophenyl thiosemicarbazone (H2Ac4oClPh), 2-acetylpyridine-N(4)-orthofluorphenyl thiosemicarbazone (H2Ac4oFPh), 2-acetylpyridine-N(4)-orthonitrophenyl thiosemicarbazone (H2Ac4oNO₂Ph), and with the corresponding 2-benzoylpyridine-derived thiosemicarbazones (H2Bz4oClPh, H2ABz4oFPh and H2Bz4oNO₂Ph). The antifungal activity of the studied compounds was evaluated against several Candida species.Upon coordination of H2Bz4oNO₂Ph to tin in complex (6) the antifungal activity increased three times against Candida albicans and Candida krusei and six times against Candida glabrata and Candida parapsilosis. The minimum inhibitory concentration (MIC) values of H2Ac4oNO₂Ph and its complex (3) against C. albicans, C. parapsilosis and C. glabrata are similar to that of fluconazole. All studied compounds were more active than fluconazole against C. krusei.     

Synthesis, characterization and antiamoebic activity of new indole-3-carboxaldehyde thiosemicarbazones and their Pd(II) complexes

In continuation of our research on thiosemicarbazones and their metal complexes as antiamoebic agents, a new series of indole-3-carboxaldehyde thiosemicarbazones (TSC) 1-7 were prepared by condensing indole-3-carboxaldehyde with cycloalkylaminothiocarbonyl hydrazines. Their palladium(II) complexes of the [Pd(TSC)Cl2] type, were synthesized upon coordination with [Pd(DMSO)2Cl2]. The chemical structures of all the compounds were established by elemental analyses, electronic, IR, (1)H NMR and (13)C NMR spectral data. The structure of the complexes was further established by thermogravimetric analysis and FAB MS. Spectroscopic data revealed that thiosemicarbazones act as bidentate ligands, making use of thione sulphur and azomethine nitrogen atom for coordination to the Pd(II) ion. Among all the compounds evaluated for antiamoebic activity using HM1:IMSS strain of Entamoeba histolytica, all palladium complexes were found to be more active than their respective ligands. Moreover, ligand 5 and complexes 1a-3a, 5a and 7a showed antiamoebic activity, at lower IC(50) doses when compared to the reference drug metronidazole with IC(50)=1.81 microM.     

In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.     

Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities

A series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UV–Vis, IR, ¹H NMR, ¹³C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners.     

Cyclooctadiene Ru(II) complexes of thiophene-2-carboxaldehyde-derived thiosemicarbazones: synthesis, characterization and antiamoebic activity

Thiosemicarbazones (TSC) 1-10 were synthesized by condensing substituted thiosemicarbazide with thiophene-2-carboxaldehyde. These thiosemicarbazones were further reacted with [Ru(eta4-C8H12)(CH3CN)2Cl2] to form complexes of the type [Ru(eta4-C8H12)(TSC)Cl2] 1a-10a. Thiosemicarbazones exhibited antiamoebic activity in the range IC50=1.09-5.42 microM. In vitro assessment of antiamoebic activity indicated that the thiosemicarbazones 3, IC50=1.67 microM, 4, IC50=1.11 microM and 6, IC50=1.09 microM showed substantially less IC50 value than metronidazole (IC50=1.87 microM), a commonly used drug against amoebiasis. Cyclooctadiene Ru(II) complexes of thiosemicarbazones showed significant improvement in antiamoebic activity (IC50=0.30-1.39 microM). All the complexes possess noteworthy potencies and showed less IC50 values than metronidazole against HK-9 strain of Entamoeba histolytica. Among all the complexes, the most promising antiamoebic activities was shown by the complexes 4a and 6a (IC50=0.31 microM of 4a and IC50=0.30 microM of 6a versus metronidazole).     

Structural and biological studies of mononuclear palladium(II) complexes containing N-substituted thiosemicarbazones

New complexes of Pd(II) with N-substituted thiosemicarbazone (1)-(3) have been synthesised and characterised by elemental analyses, IR, electronic, (1)H NMR spectroscopies. The electrochemical behaviour of the complexes has been tested by using cyclic voltammetry. The crystal structures of the complexes have been determined by single crystal X-ray diffraction technique. In all the complexes the thiosemicarbazone ligand is coordinated to palladium through ONS mode. The complex 1 crystallises in the monoclinic space group P2(1)/c with two molecules per unit cell, has the dimensions of a=9.4390(19)A, b=10.645(2)A, c=13.668(3)A, alpha=90 degrees , beta=91.43 degrees and gamma=90 degrees . The complex 3 crystallises in the monoclinic space group P2(1)/c with four molecules per unit cell, has the dimensions of a=14.119(3)A, b=11.155(2)A, c=18.503(4)A, alpha=90 degrees , beta=112.02 degrees and gamma=90 degrees . The new complexes have been tested for their antibacterial activity against various pathogenic bacteria. From this study, it was found out that the activity of the complex 2 almost reaches the effectiveness of the conventional bacteriocide Streptomycin.     

Cytotoxic copper (II) mixed ligand complexes: crystal structure and DNA cleavage activity

Two new mixed ligand complexes of copper (II) containing an imidazolyl terpyridine ligand, [Cu(Itpy)(bpy)](ClO(4))(2)·(H(2)O), 1, and [Cu(Itpy)(phen) (ClO(4))](ClO(4))·(H(2)O), 2 have been synthesized and characterized. Complex 1 has been found to possess a distorted square pyramidal geometry whereas 2 exhibit a distorted octahedral geometry. Electronic spectral titrations suggest that 1 and 2 bind to DNA intercalatively with the binding constant, K(b) (4.12 ± 0.13) × 10(4) M(-1) (1) and (6.04 ± 0.15) × 10(4) M(-1) (2). Under physiological condition, in the absence of any external cofactor 2 has been found to bring about DNA cleavage via hydrolytic mechanism but 1 does not bring about any DNA cleavage. Both compounds show antitumor effects on the A549 lung adenocarcinoma cancer cell line.     

Copper(II) complexes with substituted thiosemicarbazones of thiophene-2-carboxaldehyde: synthesis, characterization and antiamoebic activity against E. histolytica

In an effort to develop potent antiamoebic agents, a series of thiosemicarbazone (TSC) ligands 1-5 derived from thiophene-2-carboxaldehyde and N4-substituted thiosemicarbazides has been prepared and characterized using various spectroscopic techniques. Treatment of the ligands with cupric chloride produced the copper(II) complexes [Cu(TSC)2Cl2] 1a-5a where ligand bind through thionic sulfur and the azomethine nitrogen. The possible geometries of the complexes were assigned on the basis of magnetic moment, electronic and thermal patterns as well as infrared spectral studies. The thiosemicarbazones and their copper complexes were tested for their in vitro antiamoebic activity against HK-9 strain of Entamoeba histolytica and showed significant growth inhibition. The results revealed that these complexes are effective chemicals in inhibiting amoebal growth, with compound 5 (having -N(CH3)(C6H5) substituent at N4) and complexes 1a-5a being more effective than the commercial antiamoebic drug, metronidazole, based on IC50 values. These data also indicated that the compounds 3a and 5a are most effective among the complexes studied (IC50=0.26 microM of 3a and IC50=0.21 microM of 5a versus IC50=1.81 microM of metronidazole).     

Novel bidentate complexes of Cu(II) derived from 5-nitrofuran-2-carboxaldehyde thiosemicarbazones with antiamoebic activity against E. histolytica

The novel analogues of 5-nitrofuran-2-carboxaldehyde thiosemicarbazones 1-10 were synthesized and their copper(II) complexes 1a-10a were obtained by means of coordination with cupric chloride. All these compounds have been characterized by elemental analysis, IR, electronic spectra and thermogravimetric patterns while ligands have also been characterized by 1H NMR spectral studies. These copper complexes are bidentate and possess octahedral geometry around Cu(II) ion. Their antiamoebic activities were carried out to ascertain their effectiveness in comparison to their corresponding thiosemicarbazones. A number of these complexes possess noteworthy potencies towards HK-9 strain of Entamoeba histolytica in vitro. The complexes 2a-7a, 9a and 10a showed less IC50 value than metronidazole, the drug of choice for amoebiasis. Moreover, complexes 2a and 9a have shown the most promising antiamoebic activities (IC50 = 0.38 microM of 2a and IC50 = 0.34 microM of 9a versus IC50 = 1.81 microM of metronidazole). These results indicate that the metallated thiosemicarbazone may be lead molecule to inhibit growth of E. histolytica.     

Synthesis, spectral studies and in vitro antibacterial activity of steroidal thiosemicarbazone and their palladium (Pd (II)) complexes

We investigated the antibacterial activity of some new steroidal thiosemicarbazone and their Pd(II) metal complexes. Metal complexes were prepared from the reaction of steroidal thiosemicarbazone with [Pd(DMSO)(2)Cl(2)]. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazone to the metal ion, the thiosemicarbazone derivatives were obtained by the thiosemicarbazide with steroidal ketones. All the compounds have been confirmed by spectral data. The antibacterial activity of these compounds was first tested in vitro by the disk diffusion assay against two gram-positive and two gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined. The results showed that steroidal complexes are better inhibit growth as compared to steroidal thiosemicarbazones of both types of the bacteria (gram-positive and gram-negative); compound Ia is better antibacterial agent as compared to amoxicillin.     

Novel palladium(II) and platinum(II) complexes with 1H-benzimidazol-2-ylmethyl-N-(4-bromo-phenyl)-amine: structural studies and anticancer activity

[MLCl(2)] (L?=?(1H-benzimidazol-2-ylmethyl)-N-(4-bromo-phenyl)-amine; M?=?Pd & Pt) and [PdL(OH(2))(2)]?2X?zH(2)O (X?=?Br, I, z?=?2; X?=?SCN, z?=?1; X?=?NO(3), z?=?0) complexes have been synthesized as potential anticancer compounds and their structures were elucidated using elemental analysis, spectral, thermal analysis and X-ray powder diffraction. The benzimidazole (L) crystallizes in the space group P2(1)/c with a?=?8.6660(3) ?, b?=?16.6739(7) ?, c?=?9.8611(4) ? and β?=?113.505(3) ° and forms an infinite chain structure with a trans-zigzag type along the crystallographic axis "a", through the intermolecular H-bond. FT-IR and (1)H NMR studies revealed that the ligand L is coordinated to the metal ion via the pyridine-type nitrogen (N(py)) of the benzimidazole ring and secondary amino group (NH(sec)). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and (1)H NMR of the benzimidazole L and its complexes were carried out by DFT/B3LYP method combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbital (NBO) analysis and frontier molecular orbitals (FMO) were performed at B3LYP/LANL2DZ level of theory. The benzimidazole L, in comparison to its metal complexes was screened for its antibacterial activity. The complexes showed cyctotoxic effects against human breast cancer (MCF7), hepatocarcinoma (HepG(2)) and colon carcinoma cells (HCT). The platinum complex (6) exhibited a moderate antitumor activity against MCF7 with IC(50)?=?10.2?μM comparing to that reported for cis-platin 9.91?μM.     

Stereospecific ligands and their complexes. Part VII. Synthesis, characterization and in vitro antitumoral activity of platinum(II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid

Platinum(II) complexes (1-4) with bidentate N,N'-ligands, O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. DFT calculations were performed for the complexes and it was found that only one diastereoisomer could be formed. Cytotoxic activity of complexes 1-4 was determined against chronic lymphocytic leukemia cells (CLL) and compared to the activity of ligand precursors L1 · 2HCl-L4·2HCl and corresponding palladium(II) complexes, [PdCl(2)L] (L = L1-L4). The complexes were found to exhibit significantly higher antitumor activities than cisplatin on CLL cells. Cytotoxic effect of platinum(II) complexes on CLL cells was higher compared to corresponding palladium(II) complexes. In addition the mode of cell death induced by platinum(II) complexes was determined.     

Cytotoxic activity and chemical reactivity of cis-platinum(II) and trans-palladium(II) complexes with diethyl (pyridinylmethyl)phosphates

A series of square-planar platinum(II) and palladium(II) complexes of the formula cis-[PtCl2L2] and trans-[PdCl2L2] [L stands for diethyl (pyridin-2-ylmethyl)phosphate (2-pmOpe) or diethyl (pyridin-3-ylmethyl)phosphate (3-pmOpe) or diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe)] have been synthesized and tested in vitro for their cytotoxicity against mouse leukemia L1210 cells. The results indicated that the cis-platinum complexes showed superior activity than trans-palladium complexes, but lower in comparison to cisplatin. The chemical reactivity of the tested complexes has been determined in an in vitro NBP test. The platinum complexes exhibited very high chemical reactivity in NBP test, higher than cisplatin. The results showed no correlation between cytotoxicity and chemical reactivity for platinum complexes. Two platinum(II) complexes {cis-[PtCl2(2-pmOpe)2], cis-[PtCl2(3-pmOpe)2]} have been synthesized and characterized by IR, 1H NMR, 31P NMR, and elemental analysis.     

Synthesis, characterization and antimicrobial activity of Co(II), Zn(II) and Cd(II) complexes with N-benzyloxycarbonyl-S-phenylalanine

In this paper the first complexes of M(2+) ions (M(2+) = Zn(2+), Cd(2+) and Co(2+)) with N-benzyloxycarbonyl-S-phenylalaninato ligand (1-3) are described. The new complexes were characterized by means of elemental analysis, IR and UV-vis spectroscopy, molar conductivity measurements and (1)H, (13)C and (15)N NMR spectroscopy (1D and 2D). The Co(II) complex adopts an octahedral geometry, and the Zn(II) and Cd(II) complexes adopt a tetrahedral one. For the first time, the antimicrobial activity of N-benzyloxycarbonyl-S-phenylalaninato ligand (N-Boc-S-phe) and the complexes 1-3 was investigated against gram-positive: Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Bacillus subtilis and gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and two strains of the yeast Candida albicans. It was shown that the complexes were effective against most strains. The best activity was detected against the yeast C. albicans.     

Synthesis, characterization of copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II) complexes of [7-hydroxy-4-methyl-8-coumarinyl]glycine and a comparitive study of their microbial activities

A new Mannich base, [7-hydroxy-4-methyl-8-coumarinyl]glycine [MCGH(2)], has been prepared by the condensation of 7-hydroxy-4-methyl-coumarin with glycine and formaldehyde. Its conformational changes on complexation with transition metal ions [copper(II), cobalt(II), nickel(II), zinc(II) and cadmium(II)] have been studied on the basis of elemental analysis, conductivity measurements, spectral (infrared, (1)H NMR, electronic, EPR), magnetic and thermogravimetric studies. The infrared spectral studies of all the complexes reveal that the ligand has coordinated through -NH and two hydroxyl groups. The conductance data of the complexes suggest them to be non-electrolytes. Fluorescence property of the ligand and its metal complexes was studied and concluded that the ligand MCGH(2) can be a potential candidate for the determination of zinc(II) and cadmium(II) at room temperature by fluorimetric method. The antimicrobial activity of all the compounds was studied against Gram negative (Escherichia coli) and Gram positive (Bacillus cirroflagellosus) bacteria and fungi, Aspergillus niger and Candida albicans. It was observed that the coordination of metal ion has a pronounced effect on the microbial activities of the ligand. All the metal complexes have shown higher antimicrobial effect than the free ligand.     

Synthesis and characterization of new Pt(II) and Pd(II) complexes with 2-quinolinecarboxaldehyde selenosemicarbazone: cytotoxic activity evaluation of Cd(II), Zn(II), Ni(II), Pt(II) and Pd(II) complexes with heteroaromatic selenosemicarbazones

New complexes of Pt(II) and Pd(II) with 2-quinolinecarboxaldehyde selenosemicarbazone were synthesized and characterized by elemental analysis, NMR and IR spectroscopy and molar conductivity measurements. The assumed geometry of Pt(II) and Pd(II) complexes was square planar where the ligand was tridentately coordinated via the quinoline and imine nitrogen atoms and the selenium atom. The cytotoxic activity of the new Pt(II) and Pd(II) compounds, as well as of some previously synthesized Cd(II), Zn(II) and Ni(II) complexes with the same or analogous ligand, was tested against a panel of three human cancer cell lines: human cervix carcinoma cells (HeLa), human melanoma cells (FemX) and breast cancer cells (MDA-361). All investigated compounds, except Pt(II) complex, possess a strong dose-dependent cytotoxic activity of the same order of magnitude as cisplatin (CDDP). The investigation of potential of these compounds to induce HeLa cell cycle perturbations was also evaluated.     

Synthesis and characterization of cobalt(II), nickel(II), copper(II) and zinc(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

A few (1:1) and (1:2) metal complexes of cobalt(II), nickel(II), copper(II) and zinc(II) have been isolated with ligand derived from the condensation of 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine with 2-acetylpyridine (L(1)) and characterized by elemental analysis, conductivity measurements, infrared, electronic, (1)H NMR spectral data, magnetic and thermogravimetric analyses. Due to insolubility in water and most of the common organic solvents and infusibility at higher temperatures, all the complexes are thought to be polymeric in nature. A square-planar geometry was suggested for copper(II) and octahedral proposed for cobalt(II), nickel(II) and zinc(II). Some of the chemically synthesized compounds have been screened in vitro against the three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Escherichia coli) organisms. It is observed that the coordination of metal ion has pronounced effect on the microbial activities of the ligand. The metal complexes have higher antimicrobial effect than the free ligands.     

Ion-selective electrode measurements of copper(II) activity in contaminated soils

A method is presented for the use of a cupric ionselective electrode to determine the free copper activity in 0.01 M CaCl₂ soil solution extracts. Ionic strength variations and the presence of aluminum caused no significant interferences. The method was applied to 18 soils with wide-ranging copper levels. The pCu²⁺ varied between 6.33 and 12.20. Acidic soils have a very high cupric ion activity even though they are not considered to be contaminated with copper. Soils considered contaminated with respect to total copper also have free pCu²⁺ activities below 10, which is close to the toxicity threshold determined in aquatic ecotoxicological studies. All mineral soils have free copper activities close to or below the values expected from pH-dependent soil equilibration studies.     

Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione

New platinum(II) and platinum(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione and various halogen ions with general formula [PtL(2)X(2)] and [PtL(2)Cl(4)], where L is the organic ligand and X is Cl(-), Br(-), J(-), were synthesized. The molecular formulae of all the complexes were confirmed by elemental analysis, IR, (1)H, (13)C NMR spectral analyses and molar conductivity. The cytotoxic effects of these complexes were examined on some human tumor cell lines. The newly synthesized cis-[PtL(2)Cl(2)] exerted cytotoxic activity against SKW-3, MCF-7, EJ, U-266 tumor cell lines, while cis-[PtL(2)Br(2)], trans-[PtL(2)I(2)] were less active. The higher oxidation state complex cis-[PtL(2)Cl(4)] was inactive in all cell lines but in SKW-3 some augmentation of the cytotoxicity was seen after co-administration of ascorbic acid but not when treated in combination with reduced glutathione or N-acetylcysteine. A DNA-fragmentation analysis revealed that the cytotoxicity of the dichloro analogue, characterized with superior activity compared to the other complexes, is mediated by induction of apoptotic cell death.