RESUMEN

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

RESUMEN

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1-4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

RESUMEN

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones. Moreover, cationic complexes containing two lonidamine-based ligands were obtained. Antiproliferative activity was studied in vitro by MTT assays. It was shown that the increase in the stability in ligand exchange reactions does not influence cytotoxicity. At the same time, the introduction of the second lonidamine fragment approximately doubles the cytotoxicity of studied complexes. The ability to induce apoptosis and caspase activation in tumour cell MCF7 was studied by employing flow cytometry.

RESUMEN

Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5-10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr).

Asunto(s)

Microondas , Enfermedades Neurodegenerativas , Animales , Conejos , Oxindoles/farmacología , Proyectos Piloto , Presión Intraocular

RESUMEN

A series of novel organotin(IV) complexes on the base of 2-(N-3',5'-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 µM for complex 2). Furthermore, compounds 1-5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.

Asunto(s)

Antineoplásicos , Compuestos Orgánicos de Estaño , Humanos , Antioxidantes/farmacología , Compuestos Orgánicos de Estaño/farmacología , Compuestos Orgánicos de Estaño/química , Bases de Schiff/farmacología , Bases de Schiff/química , Cristalografía por Rayos X , Antineoplásicos/farmacología

RESUMEN

A novel polydentate chelating antioxidant ligand and series of organotin complexes on its base were synthesized and characterized by NMR 1H, 13C, 119Sn, IR spectroscopy, X-ray, and elemental analysis. Their antioxidant activity was evaluated in DPPH and NBT-tests, and as lipoxygenase inhibitory activity. It was shown that ligand alone is a radical scavenger, while introducing tin in the structure of the compound significantly decreases its activity. For the ligand alone the ability to strongly suppress the formation of advanced glycation end products (AGEs) was shown, which may be associated with the established antiradical activity. All synthesized compounds appeared to be moderate lipoxygenase inhibitors. The stability of compounds to hydrolysis under different pH was estimated. The ligand undergoes decomposition after about an hour, while organotin complexes on its base demonstrate vast stability, showing signs of decomposition only after 5 h of experimentation. Cytotoxicity of compounds was studied by standard MTT-test, which showed unorthodox results: the ligand itself demonstrated noticeable cytotoxicity while the introduction of organotin moiety either did not affect the toxicity levels or reduced them instead of increasing. Organotin complexes possess luminescence both as powders and DMSO solutions, its quantum yields reaching 67% in DMSO. The combination of luminescence with unique cytotoxic properties allows us to propose the synthesized compounds as perspective theranostic agents.

Asunto(s)

Antineoplásicos , Compuestos Orgánicos de Estaño , Ligandos , Antioxidantes/farmacología , Compuestos Orgánicos de Estaño/farmacología , Compuestos Orgánicos de Estaño/química , Antineoplásicos/farmacología , Espectroscopía de Resonancia Magnética

RESUMEN

The application of non-planar scaffolds in drug design allows for the enlargement of the chemical space, and for the construction of molecules that have more effective target-ligand interactions or are less prone to the development of resistance. Among the works of the last decade, a literature search revealed spirothiazamenthane, which has served as a lead in the development of derivatives active against resistant viral strains. In this work, we studied the novel molecular scaffold, which resembles spirothiazamenthane, but combines isoxazoline as a heterocycle and cyclooctane ring as a hydrophobic part of the structure. The synthesis of new 3-nitro- and 3-aminoisoxazolines containing spiro-fused or 1,2-annelated cyclooctane fragments was achieved by employing 1,3-dipolar cycloaddition of 3-nitro-4,5-dihydroisoxazol-4-ol 2-oxide or tetranitromethane-derived alkyl nitronates with non-activated alkenes. A series of spiro-sulfonamides was obtained by the reaction of 3-aminoisoxazoline containing a spiro-fused cyclooctane residue with sulfonyl chlorides. Preliminary screening of the compounds for antiviral, antibacterial, antifungal and antiproliferative properties in vitro revealed 1-oxa-2-azaspiro[4.7]dodec-2-en-3-amine and 3a,4,5,6,7,8,9,9a-octahydrocycloocta[d]isoxazol-3-amine with activity against the influenza A/Puerto Rico/8/34 (H1N1) virus in the submicromolar range, and high values of selectivity index. Further study of the mechanism of the antiviral action of these compounds, and the synthesis of their analogues, is likely to identify new agents against resistant viral strains.

Asunto(s)

Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Aminas/uso terapéutico , Antivirales/química , Ciclooctanos , Humanos , Gripe Humana/tratamiento farmacológico , Relación Estructura-Actividad

RESUMEN

This work studied the mechanism of action of a Pt(IV) complex 2 bearing two axial lonidamine ligands, which are selective inhibitors of aerobic glycolysis. The presence of two lonidamine ligands in 2 compared to the parent Pt(II) complex increased its antiproliferative activity, cellular accumulation, and changed its cell cycle profile and mechanism of cell death. In 3D cell culture, 2 showed exceptional antiproliferative activity with IC50 values as low as 1.6 µM in MCF7 cells. The study on the influence of the lonidamine ligands in the Pt complex on glycolysis showed only low potency of ligands to affect metabolic processes in cancer cells, making the investigated complex, not a dual- or multi-action prodrug. However, the Pt(IV) prodrug effectively delivers the cytotoxic Pt(II) complex into cancer cells.

Asunto(s)

Antineoplásicos , Profármacos , Antineoplásicos/farmacología , Línea Celular Tumoral , Indazoles , Ligandos , Profármacos/farmacología

RESUMEN

A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of ß-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5-trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3-methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1ab) to the androgen-sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI-26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).

Asunto(s)

Antimitóticos , Antineoplásicos , Neoplasias , Antimitóticos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , Benzamidas/farmacología , Línea Celular Tumoral , Proliferación Celular , Células Endoteliales/metabolismo , Humanos , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacología

RESUMEN

A series of bifunctional Ru(III) complexes with lonidamine-modified ligands (lonidamine is a selective inhibitor of aerobic glycolysis in cancer cells) was described. Redox properties of Ru(III) complexes were characterized by cyclic voltammetry. An easy reduction suggested a perspective for these agents as their whole mechanism of action seems to be based on activation by metal atom reduction. New compounds demonstrated a more pronounced antiproliferative potency than the parental drug; individual new agents were more cytotoxic than cisplatin. Stability studies showed an increase in the stability of complexes along with the linker length. A similar trend was noted for antiproliferative activity, cellular uptake, apoptosis induction, and thioredoxin reductase inhibition. Finally, at concentrations that did not alter water solubility, the selected new complex evoked no acute toxicity in Balb/c mice.

Asunto(s)

Indazoles/química , Rutenio/química , Rutenio/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ligandos , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Oxidación-Reducción , Relación Estructura-Actividad , Reductasa de Tiorredoxina-Disulfuro/metabolismo

RESUMEN

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS-CoV-2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain-like protease PLpro . In addition to many well-established types of mononuclear experimental metallodrugs, the pool of compounds tested was extended to approved metal-based therapeutics such as silver sulfadiazine and thiomersal, as well as polyoxometalates (POMs). Among the mononuclear metal complexes, only a small number of active inhibitors of the S/ACE2 interaction was identified, with titanocene dichloride as the only strong inhibitor. However, among the gold and silver containing complexes many turned out to be very potent inhibitors of PLpro activity. Highly promising activity against both targets was noted for many POMs. Selected complexes were evaluated in antiviral SARS-CoV-2 assays confirming activity for gold complexes with N-heterocyclic carbene (NHC) or dithiocarbamato ligands, a silver NHC complex, titanocene dichloride as well as a POM compound. These studies might provide starting points for the design of metal-based SARS-CoV-2 antiviral agents.

Asunto(s)

Antivirales/farmacología , Proteasas Similares a la Papaína de Coronavirus/antagonistas & inhibidores , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Enzima Convertidora de Angiotensina 2 , SARS-CoV-2/efectos de los fármacos

RESUMEN

BACKGROUND: Conventional antitumor Photosensitizers (PS) are normally low toxic in the dark whereas light activation triggers massive cell death (photodynamic therapy, PDT). OBJECTIVE: To expand the therapeutic potential of PS to dual potency cytocidal agents, taking advantage of the use of bacteriopurpurin for a deeper tissue penetration of light, and suitability of the tetrapyrrolic macrocycle for chemical modifications at its periphery. METHODS: Conjugation of a pro-oxidant thiolate Au (I) moiety to the bacteriopurpurin core and evaluation of cytotoxicity in cell culture and in vivo. RESULTS: New water-soluble derivatives showed micromolar cytotoxicity for cultured human tumor cell lines in the dark, including the subline with an altered drug response due to p53 inactivation. Cellular PDT with the selected conjugate, thiolate Au (I)-dipropoxybacteriopurpurinimide (compound 6) with two triphenylphosphine Au fragments, triggered rapid (within minutes) cell death. Damage to the plasma membrane (necrosis) was a hallmark of cell death by compound 6 both in the dark and upon light activation. Furthermore, one single i.v. injection of compound 6 caused retardation of transplanted syngeneic tumors at the tolerable dose. Illumination of tumors that accumulated compound 6 significantly synergized with the effect of 6 in the dark. CONCLUSION: Complexes of virtually non-toxic, photoactivatable bacteriopurpurin with the gold-containing organic moiety are considered the dual potency antitumor agents, tentatively applicable for intractable tumors.

Asunto(s)

Antineoplásicos/farmacología , Oro/farmacología , Luz , Compuestos Orgánicos de Oro/farmacología , Feofitinas/farmacología , Compuestos de Sulfhidrilo/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Muerte Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Oro/química , Células HCT116 , Humanos , Estructura Molecular , Compuestos Orgánicos de Oro/síntesis química , Compuestos Orgánicos de Oro/química , Feofitinas/química , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/química , Células Tumorales Cultivadas

RESUMEN

We present the synthesis and cytotoxic potencies of new Pt(IV) complexes with bexarotene, an anticancer drug that induces cell differentiation and apoptosis via selective activation of retinoid X receptors. In these complexes bexarotene is positioned as an axial ligand. The complex of one bexarotene ligand attached to Pt(IV) oxaliplatin moiety was potent whereas its counterpart carrying two bexarotene ligands was inactive.

RESUMEN

A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16µM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4µM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3µM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons.

Asunto(s)

Depuradores de Radicales Libres/síntesis química , Isoxazoles/síntesis química , Inhibidores de la Lipooxigenasa/síntesis química , Lipooxigenasa/metabolismo , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Antimicina A/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Línea Celular Tumoral , Depuradores de Radicales Libres/farmacología , Humanos , Isoxazoles/farmacología , Peroxidación de Lípido/efectos de los fármacos , Inhibidores de la Lipooxigenasa/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/enzimología , Neuronas/citología , Neuronas/enzimología , Oligomicinas/farmacología , Picratos/antagonistas & inhibidores , Cultivo Primario de Células , Ratas , Glycine max/química , Glycine max/enzimología , Relación Estructura-Actividad

RESUMEN

Chemotherapeutics for the treatment of tumorigenic conditions that feature novel modes of action are highly sought after to overcome the limitations of current chemotherapies. Herein, we report the conjugation of the alkylating agent chlorambucil to the RAPTA scaffold, a well-established pharmacophore. While chlorambucil is known to alkylate DNA, the RAPTA complexes are known to coordinate to amino acid side chains of proteins. Therefore, such a molecule combines DNA and protein targeting properties in a single molecule. Several chlorambucil-tethered RAPTA derivatives were prepared and tested for their cytotoxicity, stability in water and reactivity to protein and DNA substrates. The anticancer activity of the complexes is widely driven by the cytotoxicity of the chlorambucil moiety. However, especially in the cisplatin-resistant A2780R cells, the chlorambucil-functionalized RAPTA derivatives are in general more cytotoxic than chlorambucil and also a mixture of chlorambucil and the parent organoruthenium RAPTA compound. In a proof-of-principle experiment, the cross-linking of DNA and protein fragments by a chlorambucil-RAPTA derivative was observed.

Asunto(s)

Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacología , Clorambucilo/química , Complejos de Coordinación/química , ADN/química , Proteínas/química , Alquilación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Clorambucilo/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Cimenos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Cinética , Células MCF-7 , Compuestos Organometálicos/química , Proteínas/metabolismo , Ubiquitina/química , Ubiquitina/metabolismo

RESUMEN

A series of Zn, Mn, Fe, Co, and Ni complexes ([MX2L], X = Cl, OAc) of the novel di-(2-picolyl)amine ligand L with an antioxidant 2,6-di-tert-butylphenol pendant were synthesized and characterized by elemental analysis, IR, multinuclear NMR spectroscopy, MALDI-TOF mass spectrometry and the molecular structures of [ZnCl2L] and [MnCl2L] were established by X-ray crystallography. The chemical oxidation of complexes with a 2,6-di-tert-butylphenol fragment to the phenoxyl radicals was studied by means of ESR method. The antioxidant radical scavenging activity of the complexes was measured spectrophotometrically using a DPPH-test and linoleic acid peroxidation. The electron transfer reactions were examined in CUPRAC tests and as the inhibition of an enzymatic reaction involving the generation of a reactive oxygen species (superoxide radical-anion) by xanthine oxidase. The lipoxygenase (LOX) inhibition activity of the studied compounds was evaluated. The in vitro biological experiments were performed by using rat brain homogenates. The role of the phenol fragment and metal was found to be essential in antioxidant activity.

Asunto(s)

Aminas/química , Antioxidantes/síntesis química , Complejos de Coordinación/síntesis química , Fenoles/química , Ácidos Picolínicos/química , Animales , Antioxidantes/química , Encéfalo/enzimología , Encéfalo/metabolismo , Complejos de Coordinación/química , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Ligandos , Lipooxigenasa/química , Lipooxigenasa/metabolismo , Inhibidores de la Lipooxigenasa/síntesis química , Inhibidores de la Lipooxigenasa/química , Conformación Molecular , Oxidación-Reducción , Ratas

RESUMEN

The oxidative stress that is associated with the abnormal level of reactive oxygen species (ROS) is considered to be involved in the carcinogenesis process. The antioxidative defense system in the living organism regulates the toxic impact of ROS and there is strong evidence that the antioxidants prevent carcinogenesis. This review will focus on a novel approach to design synthetic metal-based antioxidants and to study their in vitro, ex vivo and in vivo activities in the cellular oxidation processes that might be involved in promotion of carcinogenesis. The antioxidants are divided into several groups depending on the nature of the ligands used: 2,6-dialkylphenols, flavonoids, polyphenols, peptides, purines, pyridines and their derivatives. Some currently achieved results in testing metal complexes as antioxidants show that they could potentially facilitate the scavenging of excess ROS, and thus restore redox balance in the damaged cells and organs. Therefore there is a strong need of the design of novel potential therapeutic candidates for prevention the oxidative stress-related carcinogenesis based on metal complexes.

Asunto(s)

Antineoplásicos/metabolismo , Antioxidantes/metabolismo , Transformación Celular Neoplásica/metabolismo , Complejos de Coordinación/metabolismo , Neoplasias/tratamiento farmacológico , Compuestos Organometálicos/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Antineoplásicos/química , Antineoplásicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Transformación Celular Neoplásica/química , Transformación Celular Neoplásica/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Flavonoides/química , Flavonoides/metabolismo , Humanos , Metales/química , Metales/metabolismo , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Péptidos/química , Péptidos/metabolismo , Polifenoles/química , Polifenoles/metabolismo , Purinas/química , Purinas/metabolismo , Piridinas/química , Piridinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

A sensitive amperometric sensor for determination of L-histidine was developed using gold electrode modified with Fe(III)-porphyrin bearing three 2,6-di-tert-butylphenol groups and one palmitoyl chain. Two methods of electrode modification were applied: direct chemisorption and embedment into dodecanethiol monolayer. Both types of electrodes were used for detection of L-histidine using Osteryoung square-wave voltammetry. The sensitivity of sensors presented towards L-histidine depends on the method of electrode modification. The detection limits observed for the electrodes incorporating with Fe(III)-porphyrin host by embedment and chemisorption were in 1 and 100 nM ranges, respectively. In addition, the determination of L-histidine with electrode modified by embedment technique was more precise, in comparison to that obtained by the direct chemisorption. Applicability of gold electrodes modified with Fe(III)-porphyrin for the direct electrochemical determination of L-histidine was demonstrated using the artificial matrix mimicking human serum.

Asunto(s)

Electroquímica/métodos , Histidina/análisis , Adsorción , Electroquímica/instrumentación , Electrodos , Oro , Hierro , Porfirinas

RESUMEN

New organotin(IV) complexes with heterocyclic thioamides 2-mercapto-benzothiazole (Hmbzt), 5-chloro-2-mercapto-benzothiazole (Hcmbzt) and 2-mercapto-benzoxazole (Hmbzo) of formulae [(C(6)H(5))(3)Sn(mbzt)] (1), [(C(6)H(5))(3)Sn(cmbzt)] (3) and [(C(6)H(5))(2)Sn(cmbzt)(2)] (4), together with the already known [(C(6)H(5))(3)Sn(mbzo)] (2), [(n-C(4)H(9))(2)Sn(cmbzt)(2)] (5) and [(CH(3))(2)Sn(cmbzt)(2)] (6) were used to study their influence on the peroxidation of oleic acid. The influence of complexes (3)-(6) upon peroxidation of oleic acid showed that the formation of reactive radicals caused the initiation of the chain radical oxidation of the substrate. The influence of complexes (1)-(6) upon the catalytic peroxidation of linoleic acid by the enzyme lipoxygenase (LOX) was also studied and compared to those of cisplatin. Compounds (1)-(6) were finally tested for in vitro cytotoxicity against leiomyosarcoma cells.

Asunto(s)

Compuestos Orgánicos de Estaño/farmacología , Tioamidas/farmacología , Catálisis , Ácido Linoleico/química , Peroxidación de Lípido , Compuestos Orgánicos de Estaño/química , Oxidación-Reducción , Tioamidas/química

RESUMEN

The in vivo effect of trimethyltin chloride (Me(3)SnCl), free base meso-tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin (R'(4)PH(2)) and their equimolar mixture, on the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), and on the total content of free sulfhydryl groups has been studied in rat liver and kidney. It was demonstrated that the simultaneous treatment of tested animals with the combination of Me(3)SnCl and R'(4)PH(2) reduced the toxic impact of Me(3)SnCl.