Patient-reported outcome measures for systemic lupus erythematosus: an expert Delphi consensus to guide implementation in routine care.

BACKGROUND: Systemic lupus erythematosus (SLE) may result in great impact on patients' quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals' and patients' perspectives. METHODS: A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2-4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. RESULTS: Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient's global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. CONCLUSIONS: Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management.

Biological assays and noncovalent interactions of pyridine-2-carbaldehyde thiosemicarbazonecopper(II) drugs with [poly(dA-dT)](2), [poly(dG-dC)] (2), and calf thymus DNA.

The interaction of the Cu(II) drugs CuL(NO(3)) and CuL'(NO(3)) (HL is pyridine-2-carbaldehyde thiosemicarbazone and HL' is pyridine-2-carbaldehyde 4N-methylthiosemicarbazone, in water named [CuL](+) and [CuL'](+)) with [poly(dA-dT)](2), [poly(dG-dC)](2), and calf thymus (CT) DNA has been probed in aqueous solution at pH 6.0, I = 0.1 M, and T = 25 degrees C by absorbance, fluorescence, circular dichroism, and viscosity measurements. The results reveal that these drugs act as groove binders with [poly(dA-dT)](2), with a site size n = 6-7, whereas they act as external binders with [poly(dG-dC)](2) and/or CT-DNA, thus establishing overall electrostatic interaction with n = 1. The binding constants with [CuL'](+) were slightly larger than with [CuL](+). The title compounds display some cleavage activity in the presence of thiols, bringing about the rupture of the DNA strands by the reactive oxygen species formed by reoxidation of Cu(I) to Cu(II); this feature was not observed in the absence of thiols. Mutagenic assays performed both in the presence and in the absence of S9 mix, probed by the Ames test on TA 98, TA 100, and TA 102, were negative. Weak genotoxic activity was detected for [CuL](+) and [CuL'](+), with a significative dose-response effect for [CuL'](+), which was shown to be more cytotoxic in the Ames test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays. Methylation of the terminal NH(2) group enhances the antiproliferative activity of the pyridine-2-carbaldehyde thiosemicarbazones.

New sulfonamide complexes with essential metal ions [Cu (II), Co (II), Ni (II) and Zn (II)]. Effect of the geometry and the metal ion on DNA binding and nuclease activity. BSA protein interaction.

Mixed divalent Cu, Co, Ni and Zn complexes containing the new sulfonamide ligand N-(2-(pyridin-2-yl)ethyl)quinoline-8-sulfonamide (HQSEP) were prepared and characterized by physico-chemical techniques. The tetracoordinate [Cu(QSEP)X] [X = Br (1), Cl (2)] compounds present a seesaw geometry (τ4 = 0.56 (1) and 0.50 (2)). The Cu(II) in the [Cu(QSEP)(NO3)(MeOH)] (3) complex is five coordinate with a slightly distorted SP geometry (τ = 0.11). The [M(QSEP)(benz)] [M = Cu(II) (4), Ni(II) (5), Co(II) (6) and Zn(II) (7); benz = benzoate] compounds are configurationally isotypic. The coordination geometries of the M(II) ions can be best described as distorted SP (τ = 0.29, 0.15, 0.34 and 0.18 for 4, 5, 6 and 7, respectively). The interaction of the compounds with CT-DNA was studied by different techniques. Notably, these studies indicated that the tetracoordinate complexes (1 and 2) present higher DNA affinity than pentacoordinate compounds (3-7). In line with the Irving-Williams order of stability, 5 presented higher propensity for DNA binding than 6. Interestingly, the cleavage activity of 1-4 in the presence of ascorbate/H2O2 follows the same trend as that found for DNA binding affinity, being the tetracoordinate 1 and 2 more effective as nucleases than the five coordinate 3 and 4. Also, the DNA cleavage reaction mechanism was investigated. DNA cleavage experiments upon irradiation indicated the important role of the aromatic nature of the coligand in the photocleavage activity of 1-4. Finally, the interaction of the compounds with bovine serum albumin (BSA) was studied and the binding constants were calculated.

In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N2-(4-nitrophenyl)-N1-propylglycinamide.

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmaniainfantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease activity assay. Both compounds showed nuclease activity in the presence of copper salt. The results suggest that compounds 4Aa, 4Ba and 5 represent possible candidates for drug development in the therapeutic control of leishmaniasis.

Copper-mediated DNA photocleavage by a tetrapyridoacridine (tpac) ligand.

We have focused our interest on the tetrapyridoacridine ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h: 2''',3'''-j]acridine (tpac), as a model system for the preparation of novel copper-based artificial nucleases. The complex of copper(II)-tpac cleaves supercoiled pUC18 plasmid DNA in an oxidative manner by photoactivation with visible light, exhibiting maximum cleaving efficiency at 1:2 metal-ligand stoichiometric ratio. We propose an interaction of the copper-tpac complex with DNA through both major and minor grooves and a photocleavage mechanism via the formation of hydroxyl radicals and singlet oxygen or singlet oxygen-like species.

Revisiting the thiosemicarbazonecopper(II) reaction with glutathione. Activity against colorectal carcinoma cell lines.

Thiosemicarbazones (TSCs), and their copper derivatives, have been extensively studied mainly due to the potential applications as antitumor compounds. A part of the biological activity of the TSC-CuII complexes rests on their reactivity against cell reductants, as glutathione (GSH). The present paper describes the structure of the [Cu(PTSC)(ONO2)]n compound (1) (HPTSC=pyridine-2-carbaldehyde thiosemicarbazone) and its spectroscopic and magnetic properties. ESI studies performed on the reaction of GSH with 1 and the analogous [{Cu(PTSC*)(ONO2)}2] derivative (2, HPTSC*=pyridine-2-carbaldehyde 4N-methylthiosemicarbazone) show the absence of peaks related with TSC-Cu-GSH species. However GSH-Cu ones are detected, in good agreement with the release of CuI ions after reduction in the experimental conditions. The reactivity of 1 and 2 with cytochrome c and myoglobin and their activities against HT-29 and SW-480 colon carcinoma cell lines are compared with those shown by the free HPTSC and HPTSC* ligands.

DNA interaction of new copper(II) complexes with sulfonamides as ligands.

New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.

Oxidative DNA cleavage induced by an iron(III) flavonoid complex: synthesis, crystal structure and characterization of chlorobis(flavonolato)(methanol) iron(III) complex.

A flavonol iron(III) complex, [Fe(flavonolato)(2)Cl(MeOH)], has been prepared. The compound has been characterized by X-ray crystallography, spectroscopy, magnetism and electronic paramagnetic resonance (EPR) at X- and Q-band. The geometrical environment around the metal is best described as rhombic distorted octahedral. This distortion has also been inferred from the magnetic measurements and from the EPR spectra at different temperatures, E/D(rhombicity parameter) approximately 0.06. The DNA cleavage activity of the iron(III) complex with and without ascorbate/hydrogen peroxide is reported. Mechanisms of the oxidative cleavage have been proposed when DNA strand scission is performed both with and without ascorbate/hydrogen peroxide activation.

Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring.

BACKGROUND: Data on long-term central nervous system (CNS) toxicity associated with efavirenz therapy are scarce, and risk factors remain largely unknown. We aimed to determine whether monitoring the plasma concentration of efavirenz could predict neuropsychiatric adverse events associated with long-term therapy with efavirenz. METHODS: We performed a longitudinal study involving 17 consecutive human immunodeficiency virus (HIV)-infected subjects with virological suppression after at least 6 months of antiretroviral therapy with an efavirenz-containing regimen. Efavirenz plasma concentrations were measured at study entry and at different time points through an 18-month study period. RESULTS: Median duration of efavirenz therapy before study entry was 18 months (range, 6-27 months). Ten (58.8%) of the patients experienced CNS-related adverse effects, ranging from insomnia and abnormal dreams to depression with suicidal ideation. In 4 (23.5%) of the cases, CNS toxicity led to efavirenz discontinuation. Mean (+/- standard deviation) plasma levels were higher for patients experiencing neuropsychiatric symptoms (5.10 +/- 2.15 microg/mL vs. 2.79 +/- 1.31 microg/mL; P = .024). A plasma level of 2.74 microg/mL had a sensitivity of 90.9% and specificity of 72% to predict CNS toxicity (area under the curve, 0.839; 95% confidence interval, 0.73-0.95; P < .0001). Patients having efavirenz plasma concentrations > 2.74 microg/mL at any time point of the study were 5.68 times more likely to experiencing CNS toxicity than were other patients (95% confidence interval, 1.97-16.37). CONCLUSIONS: In patients with HIV infection receiving long-term therapy with efavirenz-containing antiretroviral regimens, CNS toxicity is related to efavirenz plasma levels. Patients achieving higher plasma levels are at increased risk of experiencing neuropsychiatric adverse events.

Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving disulfiram therapy.

Disulfiram is widely used in the treatment of chronic alcoholism. Adverse drug reactions with fatal outcome following disulfiram therapy are infrequent, and hepatic failure accounts for most of them. Since disulfiram is a cytochrome P450 (CYP450) enzyme system inhibitor, numerous interactions with several drugs metabolized in the liver have been reported. Like disulfiram, clarithromycin inhibits a CYP450 isoenzyme, but, despite its widespread use for the treatment of respiratory tract infections, no interactions with disulfiram have been described as yet. We report a case of fatal toxic epidermal necrolysis (Lyell disease) and fulminant hepatitis shortly after starting treatment with clarithromycin in a patient who was receiving disulfiram. This is the first case of such a severe dermatosis in a patient receiving either disulfiram or clarithromycin therapy. The temporal relationship between drug administration and clinical symptoms in this case suggests a probable interaction between the 2 drugs.

Spectroscopic, Magnetic, and Electrochemical Studies of a Dimeric N-Substituted-Sulfanilamide Copper(II) Complex. X-ray and Molecular Structure of the Cu(2)(sulfathiazolato)(4) Complex.

A copper(II) complex of formula Cu(2)(stz)(4) (stz(-) = sulfathiazolato) has been synthesized and characterized by single-crystal X-ray diffraction. The compound crystallizes in the orthorhombic system, space group P2(1)cn with a = 10.595(7) Å, b = 14.274(3) Å, c = 29.65(1) Å, and Z = 4. The structure consists of dinuclear copper(II) units which contain four sulfathiazolato ligands bridging the metal ions through a nonlinear NCN group. The copper atoms are four-coordinated, the chromophore being CuN(4). The Cu.Cu bond distance is 2.671(2) Å. Magnetic susceptibility data in the temperature range 7-300 K show the occurrence of intramolecular antiferromagnetic coupling with 2J = -61.5 cm(-1). This low exchange energy value has been analyzed and rationalized through extended Hückel calculations. EPR spectra at X- and Q-band frequencies show the signals corresponding to a dinuclear entity, being the zero-field splitting parameter, D = 0.230 cm(-1).

Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)]: study of its interaction with DNA and hydrogen peroxide.

A new copper complex with N-quinolin-8-yl-p-toulenesulfonamide has been prepared and characterised. The compound crystallises in the triclinic system, space group P1, with a=13.457(3), b=15.067(5), c=18.589(3) A; alpha=112.05(2), beta=93.92(2), gamma=108.30(2) degrees and Z=4. The geometry of the Cu(II) ion is distorted square planar. The N-quinolin-8-yl-p-toulenesulfonamidate anion behaves as a bidentate ligand through the N(sulfonamidate)and N(quinoline) atoms. The complex does not cleave DNA in the presence of hydrogen peroxide.

Syntheses, crystal structures, and oxidative DNA cleavage of some Cu(II) complexes of 5-amino-3-pyridin-2-yl-1,2,4-triazole.

Three new monomeric Cu(II) complexes of 5-amino-3-pyridin-2-yl-1,2,4-triazole (Hapt), [Cu(Hapt)(H(2)O)(2)(SO(4))] (1), [Cu(Hapt)(2)(H(2)O)(NO(3))](NO(3)) (2), and [Cu(Hapt)(2)(NCS-N)](NCS).H(2)O (3), have been prepared and characterized by single crystal X-ray diffraction. One distorted [CuN(2)O(2)+O(')] square-pyramidal (1), one distorted [CuN(3)O+N(')+O(')] octahedral (2), and one distorted [CuN(4)+N(')] intermediate between square-pyramidal and trigonal-bipyramidal (3) coordination configuration were found and are suggested to be due to the chelating nature of the ligand, which interacts with Cu(II) through the N4(triazole) and N(pyridine) atoms. Spectral properties of these chelates are in accordance with the X-ray structural data. With ascorbate and H(2)O(2) activation, compound 2 exhibits higher nuclease activity than compound 1. The influence on the DNA cleavage process of different scavengers of reactive oxygen species: dimethyl sulfoxide (DMSO), tert-butyl alcohol, sodium azide, 2,2,6,6-tetramethyl-4-piperidone and superoxide dismutase enzyme (SOD), and of the minor groove binder distamycin, is also studied.

Oxidative DNA damage of mixed copper(II) complexes with sulfonamides and 1,10-phenanthroline. Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)2(1,10-phenanthroline)].

Mixed coordination compounds of Cu(II) with sulfonamides and 1,10-phenanthroline as ligands have been prepared and characterised. Single crystal structural determination of the complex [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)(phen)] shows Cu(II) ions are located in a highly distorted octahedral environment, probably as a consequence of the Jahn-Teller effect. The FT-IR and electronic paramagnetic resonance (EPR) spectra are also discussed. The mixed complexes prepared undergo an extensive DNA cleavage in the presence of ascorbate and hydrogen peroxide. Two of the complexes have higher nucleolytic efficiency than the bis(o-phenanthroline)copper(II) complex.

Structural and functional models for the dinuclear copper active site in catechol oxidases. Synthesis, X-ray crystal structures, magnetic and spectroscopic properties of mu-methoxo-bridged dinuclear copper(II) complexes with N-substituted sulfonamide ligands.

Two new mu-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(mu-OMe)(L)(NH(3))](2) (1) and [Cu(mu-OMe)(L)(DMSO)](2) (2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C(2)/c with a=22.0678(18), b=7.9134(7), c=21.1186(18)A, beta=113.788(4) degrees and Z=8. Compound 2 crystallizes in the monoclinic space group C(2)/c with a=18.0900(10), b=9.5720(10), c=24.2620(10) A, beta=98.7120(10) degrees and Z=8. In both complexes the copper atoms have square-planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2J<-1000 cm(-1)). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di-tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.

Strong protective action of Copper(II) N-substituted sulfonamide complexes against reactive oxygen species.

Copper(II) complexes of N-benzothiazolsulfonamides, [Cu(N-2-(5,6-dimethylbenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (1), [Cu(N-2-(6-chlorobenzothiazole)benzenesulfonamidate)(2)(dmso)(2)] (2) and [Cu(N-2-(6-chlorobenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (3) with interesting protective properties against superoxide radicals have been prepared. The compounds have been characterized by X-ray diffraction and their chemical properties have been studied by spectroscopic methods. The crystal structure of 1 shows that the copper(II) is surrounded by two benzothiazole N atoms from the sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a square planar arrangement. The coordination polyhedron around copper(II) in 2 and 3 is distorted square pyramidal being the metal ion linked to benzothiazole N and sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The three complexes have a strong protective action over Delta sod1 mutant of Saccharomyces cerevisiae against reactive oxygen radicals derived from respiration and against those generated by hydrogen peroxide and menadione.

Complexes of Co(II) and Zn(II) with ofloxacin. Crystal structure of [Co(oflo)2(MeOH)2].4MeOH.

Ofloxacin (oflo) is able to interact with Co(II) and Zn(II) salts to form complexes with the general formula [M(oflo)(2)]. 4H(2)O, (M = Co, Zn). Bonding takes place through one of the oxygen atoms of the carboxylate group (acting as a monodentate) and the oxygen atom of the ketonic group. The IR bands of the carboxylic and ketonic group at 1713 and 1622 cm(-1), respectively, shift to 1615 and 1575 cm(-1) in the complexes. After dissolution in methanol, complex [Co(oflo)(2)]. 4H(2)O crystallizes as [Co(oflo)(2)(MeOH)(2)]. 4MeOH, where Co(II) ion is in an octahedral environment of oxygen atoms. This compound crystallizes in the triclinic system, spatial group P-1, with unit cell dimensions a = 9.3670(12), b = 11.4135(17), c = 11.851(2) A y alpha = 71.999(14), beta = 73.698(12), gamma = 83.528(14) degrees. Magnetic properties (effective magnetic moment 5.02 BM) and visible spectrum (bands at 490, 510, and 1152 nm) are characteristic of such an octahedral geometry. (1)H- and (13)C-NMR spectra of the Zn(II) complex indicate only small structural changes in ofloxacin upon coordination to the metallic site.

DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties of Cu(II) complexes of N-substituted sulfonamides.

Ternary copper(II) complexes [Cu(NST)2(phen)] (1) and [Cu(NST)2(NH3)2]·H2O (2) [HNST=N-(4,5-dimethylthiazol-2-yl)naphthalene-1-sulfonamide] were prepared and characterized by physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square planar CuN4 geometry in which the deprotonated sulfonamide, acting as monodentate ligand, binds to the metal ion through the thiazole N atom. Both complexes present intermolecular π-π stacking interactions between phenanthroline rings (compound 1) and between naphthalene rings (compound 2). The interaction of the complexes with CT DNA was studied by means of thermal denaturation, viscosity measurements and fluorescence spectroscopy. The complexes display good binding propensity to the calf thymus DNA giving the order: 1>2. Complex 1, which has a higher capability for binding to DNA, showed better nuclease activity than 2 in the presence of ascorbate/H2O2. Both the kinetics and the mechanism of the DNA cleavage reaction were investigated. Furthermore, complex 1 showed efficient photo-induced DNA cleavage activity on irradiation with UV light in the absence of any external reagent. The UV light induced DNA cleavage follows a photo-redox pathway with generation of hydroxyl radicals as reactive species. In addition, the cytotoxic properties of both complexes (1 and 2) were evaluated in human cancer cells (HeLa, Caco-2 and MDA-468). The low IC50 values, in particular those against Caco-2, have indicated that the compounds can be considered as promising chemotherapeutic agents.

Mixed-ligand copper(II)-sulfonamide complexes: effect of the sulfonamide derivative on DNA binding, DNA cleavage, genotoxicity and anticancer activity.

Four ternary complexes, [Cu(L1)2(bipy)] (1) [HL1 = N-(6-chlorobenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], [Cu(L2)2(bipy)] (2) [HL2 = N-(benzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], [Cu(L3)2(bipy)]·1/2H2O (3) [HL3 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide] and [Cu(L4)2(bipy)] (4) [HL4 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)benzenesulfonamide], were prepared and then characterized by X-ray crystallography, spectroscopy and magnetic measurements. Whereas the molecular structure of 1 and 2 consists of a discrete monomeric copper(II) species with a distorted square planar geometry, that of 3 and 4 consists of two independent molecules. In 3, both molecules present a different coordination geometry (distorted square planar and distorted square pyramidal) while in 4 they have an identical coordination environment (distorted square planar). The propensity for binding of 1-4 to calf thymus DNA was studied by thermal denaturation, viscosimetry, and fluorescence measurements. Results indicated that the N-sulfonamide derivative plays an important role in governing the type of interaction with DNA. The ability of the complexes to cleave DNA was studied in vitro with ascorbate activation and was tested by monitoring the expression of the yEGFP gene containing the RAD54 reporter. Moreover, their antiproliferative activity was verified in two cellular models: yeast and human tumor cells in culture. Their DNA cleavage efficiency at the cellular level was found to be: 1 < 3 ~ 4 < 2. The higher propensity of 2 for inflicting DNA damage was related with its higher binding affinity to DNA. The biological studies carried out with human tumor cells, colon adenocarcinoma Caco-2 cells and leukemia Jurkat T lymphocytes confirmed that the compounds produce cell death mainly by apoptosis, the complex 2 being the most effective.