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1.
Molecules ; 25(17)2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32847116

RESUMO

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)-Au(I) dinuclear complexes were synthesized; they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)-Au(I) complex not functionalized with carbohydrates.

2.
Molecules ; 25(8)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316698

RESUMO

Three new 6-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-thiosemicarbazones-N-4-substituted pro-ligands and their Cu(II) complexes (1, -NH2; 2, -NHMe; 3, -NHEt) have been prepared and characterized. In both the X-ray structures of 1 and 3, two crystallographically independent complex molecules were found that differ either in the nature of weakly metal-binding species (water in 1a and nitrate in 1b) or in the co-ligand (water in 3a and methanol in 3b). Electron Paramagnetic Resonance (EPR) measurements carried out on complexes 1 and 3 confirmed the presence of such different species in the solution. The electrochemical behavior of the pro-ligands and of the complexes was investigated, as well as their biological activity. Complexes 2 and 3 exhibited a high cytotoxicity against human tumor cells and 3D spheroids derived from solid tumors, related to the high cellular uptake. Complexes 2 and 3 also showed a high selectivity towards cancerous cell lines with respect to non-cancerous cell lines and were able to circumvent cisplatin resistance. Via the Transmission Electron Microscopy (TEM) imaging technique, preliminary insights into the biological activity of copper complexes were obtained.

3.
Materials (Basel) ; 12(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779206

RESUMO

From the well-known 1,3,5-triaza-phosphaadamantane (PTA, 1a), the novel N-allyl and N-benzyl tetrafuoroborate salts 1-allyl-1-azonia-3,5-diaza-7-phosphaadamantane (APTA(BF4), 1b) and 1-benzyl-1-azonia-3,5-diaza-7-phosphaadamantane (BzPTA(BF4), 1c) were obtained. These phosphines were then allowed to react with (Pt(µ-Cl)(C6F5)(tht))2 (tht = tetrahydrothiophene) affording the water soluble Pt(II) complexes trans-(PtCl(C6F5)(PTA)2) (2a) and its bis-cationic congeners trans-(PtCl(C6F5)(APTA)2)(BF4)2 (2b) and trans-(PtCl(C6F5)(BzPTA)2)(BF4)2 (2c). The compounds were fully characterized by multinuclear NMR, ESI-MS, elemental analysis and (for 2a) also by single crystal X-ray diffraction, which proved the trans configuration of the phosphine ligands. Furthermore, in order to evaluate the cytotoxic activities of all complexes the normal human dermal fibroblast (NHDF) cell culture were used. The antineoplastic activity of the investigated compounds was checked against the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and breast adenocarcinoma (MCF-7) cell cultures. Interactions between the complexes and human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism spectroscopy (CD) were also investigated.

4.
Cells ; 8(11)2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31752448

RESUMO

Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell-cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell-cell and cell-ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

5.
Dalton Trans ; 48(35): 13491-13492, 2019 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453993

RESUMO

Correction for 'New light on an old debate: does the RCN-PtCl2 bond include any back-donation? RCN ← PtCl2 backbonding vs. the IR νC[triple bond, length as m-dash]N blue-shift dichotomy in organonitriles-platinum(ii) complexes. A thorough density functional theory - energy decomposition analysis study' by Girolamo Casella et al., Dalton Trans., 2019, DOI: 10.1039/c9dt02440a.

6.
Dalton Trans ; 48(34): 12974-12985, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31397469

RESUMO

For a series of organonitrile [RCN (R = Me, CF3, Ph, CH3Ph, CF3Ph)] ligands, the nature of the N-Pt bond in the related cis-/trans-(RCN)2PtCl2 complexes has been computationally investigated by Density Functional Theory. A fragment based bond analysis has been performed in the canonical Kohn-Sham molecular orbitals framework, and it has been ultimately assessed that this bond is characterized both by N→Pt σ and by N←Pt π contributions. Voronoi Deformation Density charges further confirms the occurrence of N←Pt π interactions. Moreover, the Energy Decomposition Analysis-Natural Orbital for Chemical Valence (EDA-NOCV) method shows that the strength of the N←Pt π interaction is not negligible by contributing to about 30-40% of the total orbital interaction. Finally, the well-known νC[triple bond, length as m-dash]N blue-shift occurring upon coordination to PtII, has been thoroughly investigated by exploiting the EDA-NOCV and by evaluating νC[triple bond, length as m-dash]N and force constants. The origin of the νC[triple bond, length as m-dash]N blue-shift in these systems has been discussed on the basis of the CN bond polarization. N←Pt π backbonding causes only a systematic decrease of the observed νC[triple bond, length as m-dash]N blue-shift when compared to the one calculated for RCN-X (X = H+, alkaline, Lewis acids) herein reported (X = purely σ acceptors).

7.
Molecules ; 24(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234368

RESUMO

The synthesis of heterobimetallic complexes remains a synthetic challenge in the field of organometallic chemistry. A possible approach in this regard might be the use of a bidentate heteroditopic bis(carbene) ligand that combines an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by an organic spacer. The optimized strategy to heterobimetallic complexes with this type of ligand involves a 3-step procedure: (i) Coordination of the nNHC, functionalized with a 1,2,3-triazole ring, to a metal center; (ii) formation of the triazolium ring by alkylation of the triazole N-3; (iii) deprotonation of the tzNHC precursor and coordination of the second metal center. Following this procedure, a novel Au(I)-Ag(I) dinuclear complex was isolated and its properties were compared to the analogous homobimetallic Ag(I)-Ag(I) and Au(I)-Au(I) complexes. The study was completed by the determination of the molecular structures of some synthetic intermediates.


Assuntos
Complexos de Coordenação/síntese química , Ouro/química , Metano/análogos & derivados , Prata/química , Alquilação , Complexos de Coordenação/química , Compostos Heterocíclicos/química , Imidazóis/química , Ligantes , Metano/química , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/química , Triazóis/química
8.
Bioelectrochemistry ; 125: 15-24, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30196014

RESUMO

Electroporation of cells is usually studied using cell suspensions or monolayer cultures. 3D scaffolds for cell culture have been recently designed in order to reproduce in vitro the complex and multifactorial environment experimented in vivo by cells. In fact, it is well known that 2D cell cultures are not able to simulate the complex interactions between the cells and their extracellular matrix (ECM). Recently, some examples of 3D models, like spheroids, have been investigated also in the electroporation field. Spheroids have been proposed in electrochemotherapy (ECT) studies to mimic tumor in vivo conditions: they are easy-to-handle 3D models but their sensitivity to electric field pulses depends from their diameter and, more interestingly, despite being relevant for intercellular junctions, they are not so much so for cell-ECM interactions. In this work, we propose a 3D macroscopic myxoid matrix for cell culture that would mimic the in vivo environment of myxoid stroma tumors. The myxoid stroma consists of abundant basic substances with large amounts of glycosaminoglycans (hyaluronic acid) and proteoglycans, poor collagen fibers and no elastin content. In the proposed approach, tumor cells seeded on 3D scaffolds mimic of myxoid stroma can establish both cell-cell and cell-ECM 3D interactions. The MCF7 cells (human breast adenocarcinoma cell line) were seeded in complete culture medium. Cell cultures were incubated at 37 °C for either 24 h, 3 days or 7 day. Some samples were used to assess cell vitality using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test and others for electroporation tests and for histopathological analysis. The electroporation has been verified by the fluorescent dye Propidium cellular uptake. The proposed myxoid stroma scaffold induces cell proliferation and shows fibrous structures produced by cells, the concentration of which increases with culture time. The proposed matrix will be used for further investigations as a new scaffold for cell culture. Tumor cells grown into these new scaffolds will be used to evaluate electroporation including the stroma effect.


Assuntos
Técnicas de Cultura de Células/métodos , Eletroporação/métodos , Tecidos Suporte/química , Microambiente Tumoral , Adenocarcinoma/química , Adenocarcinoma/patologia , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Técnicas de Cultura de Células/instrumentação , Proliferação de Células , Sobrevivência Celular , Eletroporação/instrumentação , Desenho de Equipamento , Feminino , Glicosaminoglicanos/química , Humanos , Ácido Hialurônico/química , Células MCF-7 , Proteoglicanas/química
9.
Technol Cancer Res Treat ; 17: 1533033818789693, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30045667

RESUMO

Electrochemotherapy is an established treatment option for patients with superficially metastatic tumors, mainly malignant melanoma and breast cancer. Based on preliminary experiences, electrochemotherapy has the potential to be translated in the treatment of larger and deeper neoplasms, such as soft tissue sarcomas. However, soft tissue sarcomas are characterized by tissue inhomogeneity and, consequently, by variable electrical characteristic of tumor tissue. The inhomogeneity in conductivity represents the cause of local variations in the electric field intensity. Crucially, this fact may hamper the achievement of the electroporation threshold during the electrochemotherapy procedure. In order to evaluate the effect of tissue inhomogeneity on the electric field distribution, we first performed ex vivo analysis of some clinical cases to quantify the inhomogeneity area. Subsequently, we performed some simulations where the electric field intensity was evaluated by means of finite element analysis. The results of the simulation models are finally compared to an experimental model based on potato and tissue mimic materials. Tissue mimic materials are materials where the conductivity can be suitably designed. The coupling of computation and experimental results could be helpful to show the effect of the inhomogeneity in terms of variation in electric field distribution and characteristics.


Assuntos
Sarcoma/patologia , Simulação por Computador , Condutividade Elétrica , Eletroquimioterapia/métodos , Eletroporação/métodos , Análise de Elementos Finitos , Humanos , Modelos Teóricos
10.
Waste Manag ; 75: 372-383, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29395732

RESUMO

The storage capacity and the potentially residual emissions of a stabilized waste coming from a landfill simulation experiment were evaluated. The evolution in time of the potential emissions and the mobility of some selected elements or compounds were determined, comparing the results of the stabilized waste samples with the values detected in the related fresh waste samples. Analyses were conducted for the total bulk waste and also for each identified category (under-sieve, kitchen residues, green and wooden materials, plastics, cellulosic material and textiles) to highlight the contribution of the different waste fractions in the total emission potential. The waste characterization was performed through analyses on solids and on leaching test eluates; the chemical speciation of carbon, nitrogen, chlorine and sulfur together with the partitioning of heavy metals through a SCE procedure were carried out. Results showed that the under-sieve is the most environmentally relevant fraction, hosting a consistent part of mobile compounds in fresh waste (40.7% of carbon, 44.0% of nitrogen, 47.6% of chloride and 40.0% of sulfur) and the greater part of potentially residual emissions in stabilized waste (88.4% of carbon, 90.9% of nitrogen, 98.4% of chloride and 91.1% of sulfur). Landfilled Municipal Solid Waste (MSW) proved to be an effective sink, finally storing more than 55% of carbon, 53% of nitrogen, 33% of sulfur and 90% of heavy metals (HM) which were initially present in fresh waste samples. A general decrease in leachable fractions from fresh to stabilized waste was observed for each category. Tests showed that solid waste is not a good sink for chlorine, whose residual non-mobile fraction amounts to 12.3% only.


Assuntos
Eliminação de Resíduos , Instalações de Eliminação de Resíduos , Metais Pesados/análise , Nitrogênio/análise , Resíduos Sólidos
11.
J Inorg Biochem ; 182: 18-28, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29407866

RESUMO

Three new 2-oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde terminal substituted aroylhydrazone ligands (2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2'-hydroxybenzoyl)hydrazine, H2L1, 1, 2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2'-hydroxybenzoyl)hydrazine, H2L2, 2, 2-Oxo-1,2-dihydrobenzo[h]quinoline-3-carbaldehyde(2'-hydroxybenzoyl)hydrazine, H2L3, 3) and the corresponding novel copper(II) complexes [Cu(L)(CH3OH)(NO3)](L = HL1 (4), HL2 (5), HL3 (6-6+), have been synthesized to compare their coordination behaviour and biological activity with respect to the presence of an OH group in different positions of the phenyl ring in the hydrazone moieties. The new ligands and their copper complexes were characterized by elemental analysis and spectroscopic techniques. The molecular structures of the new complexes 4 and 6-6+ were determined by single crystal X-ray diffraction. The interactions of the free ligands and their copper complexes with calf thymus DNA were tested by absorption measurements and ethidium bromide competitive studies which revealed that all compounds may interact with calf thymus DNA through intercalation. Furthermore, a comparative analysis of the cytotoxic effect of the compounds on a panel of human cancer cell lines showed that the copper complexes exhibited in vitro antitumor activity significantly higher than that of the free ligands and also of cisplatin.


Assuntos
Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cobre/química , Compostos Organometálicos/síntese química , Compostos Organometálicos/toxicidade , Quinolinas/química , Linhagem Celular Tumoral , Complexos de Coordenação/química , DNA/efeitos dos fármacos , DNA/genética , Clivagem do DNA/efeitos dos fármacos , Células HCT116 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Compostos Organometálicos/química , Plasmídeos
12.
Nanomaterials (Basel) ; 7(11)2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29113079

RESUMO

Ferrofluids are nanomaterials consisting of magnetic nanoparticles that are dispersed in a carrier fluid. Their physical properties, and hence their field of application are determined by intertwined compositional, structural, and magnetic characteristics, including interparticle magnetic interactions. Magnetic nanoparticles were prepared by thermal decomposition of iron(III) chloride hexahydrate (FeCl3·6H2O) in 2-pyrrolidone, and were then dispersed in two different fluids, water and polyethylene glycol 400 (PEG). A number of experimental techniques (especially, transmission electron microscopy, Mössbauer spectroscopy and superconducting quantum interference device (SQUID) magnetometry) were employed to study both the as-prepared nanoparticles and the ferrofluids. We show that, with the adopted synthesis parameters of temperature and FeCl3 relative concentration, nanoparticles are obtained that mainly consist of maghemite and present a high degree of structural disorder and strong spin canting, resulting in a low saturation magnetization (~45 emu/g). A remarkable feature is that the nanoparticles, ultimately due to the presence of 2-pyrrolidone at their surface, are arranged in nanoflower-shape structures, which are substantially stable in water and tend to disaggregate in PEG. The different arrangement of the nanoparticles in the two fluids implies a different strength of dipolar magnetic interactions, as revealed by the analysis of their magnetothermal behavior. The comparison between the magnetic heating capacities of the two ferrofluids demonstrates the possibility of tailoring the performances of the produced nanoparticles by exploiting the interplay with the carrier fluid.

13.
Des Monomers Polym ; 20(1): 547-563, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29491826

RESUMO

In order to prepare thermally stable isosorbide-derived thermoplastic polyurethane, the synthesis of two new chiral exo-exo configured diols, prepared from isosorbide, and two types of diphenols (bisphenol A and thiodiphenol) was described. The synthesis conditions were optimized under conventional heating and microwave irradiations. To prove their suitability in polymerization, these monomers were successfully polymerized using 4,4'-diphenylmethane diisocyanate (MDI) and hexamethylene diisocyanate (HDI). Both monomers and polymers have been studied by NMR, FT-IR, TGA, DSC; intrinsic viscosity of polymers has also been determined. The results showed the effectiveness of the synthetic strategy proposed; moreover, a dramatic reduction of the reaction time and an important improvement of the monomers yield using microwave irradiation have been demonstrated. The monomers, as well as the polymers, showed excellent thermal stability both in air and nitrogen. It was also shown that the introduction of sulphur in the polyurethane backbone was effective in delaying the onset of degradation as well as the degradation rate.

14.
Nanotechnology ; 27(28): 285104, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27265726

RESUMO

Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar (1)H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.

15.
Dalton Trans ; 45(23): 9540-52, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27193490

RESUMO

Three novel dinuclear bis-dicarbene silver(i) complexes of general formula [Ag2(MeIm-phenylene-MeIm)2](PF6)2 (Im = imidazol-2-ylidene) were synthesized. The corresponding copper(i) and gold(i) complexes were obtained by transmetalation of the di(N-heterocyclic carbene) ligand from the silver(i) species, and both coordination geometry and stoichiometry are maintained for all three group 11 metals as expected. The photophysical properties of the Ag(i) and Au(i) complexes were also investigated and discussed; in particular the most strongly emitting complex was also studied via DFT calculations. In addition, the ruthenium(ii) and iridium(iii) complexes [RuCl(MeIm-(o-phenylene)-MeIm)(p-cym)](PF6) and [IrClCp*(MeIm-(o-phenylene)-MeIm)](PF6) were prepared and shown to present in these cases a chelating coordination of the di(N-heterocyclic carbene) ligand.

16.
J Inorg Biochem ; 155: 1-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26606287

RESUMO

A novel binuclear palladium(II) complex [(AsPh3)2ClPd(L)PdCl] (LPd2) has been synthesized by reacting 2-oxo-1,2-dihydroquinoline-3-carbaldehyde-4(N,N)-dimethylthiosemicarbazone (HL) with [PdCl2(AsPh3)2], and the molecular structure was confirmed by single crystal X-ray diffraction studies. The DNA interactions of the free ligand and of the complex have been evaluated by absorption and ethidium bromide (EB) competitive studies which revealed that the complex could interact with calf thymus DNA (CT-DNA) through intercalation. In addition, the interactions with bovine serum albumin (BSA) were also studied showing that the new binuclear palladium complex had a strong binding affinity with BSA.


Assuntos
DNA/química , Paládio/química , Proteínas/química , Tiossemicarbazonas/química , Cristalografia por Raios X , Ligação Proteica
17.
Cutan Ocul Toxicol ; 35(4): 332-6, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26612003

RESUMO

Hair highlights are quite common procedures carried out in hair salons by using a mixture of a lightening powder containing persulfates with a suspension containing hydrogen peroxide: a representative case of chemical scalp burns is described as a consequence of this treatment. The aim of the paper is to demonstrate the strict relationship between the scalp damage and the commercial products used in a case of hair highlighting. The results of some chemical analyses have been reported, showing, in particular, that the chemical reactivity of the mixture changes in the time, thus strongly suggesting that the procedure for the application of the mixture is critical for the occurrence of possible accidents. The presence in the powder of chemical compounds bearing aliphatic chains as surfactants explains the appearance of dramatic symptoms after days due to a slow dissolution of the oxidant compounds in the stratum corneum of skin with no effect in reducing injury of palliative treatments. Safety suggestions and recommendations for producers and workers are also included.


Assuntos
Queimaduras Químicas/etiologia , Tinturas para Cabelo/toxicidade , Couro Cabeludo/efeitos dos fármacos , Adulto , Queimaduras Químicas/cirurgia , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Oxidantes/toxicidade , Couro Cabeludo/lesões , Couro Cabeludo/cirurgia , Sulfatos/toxicidade
18.
Chemistry ; 21(1): 440-7, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25353654

RESUMO

Herein a combined NOE NMR/DFT methodology to discriminate between adducts held together by halogen bonding (XB) and other noncovalent interactions (non-XB, such as lone pair/π), based on the determination of the XB donors' and acceptors' relative orientation, is proposed. In particular, (19) F,(1) H HOESY NMR spectroscopy experiments and DFT calculations on different XB donors, such as perfluorohexyl iodide (I1), iodopentafluorobenzene (I2) and bromopentafluorobenzene (Br), combined with different Lewis bases, such as 1,4-diazabicyclo[2.2.2]octane (DABCO) and 2,4,6-trimethylpyridine (Me3 Py), were performed. The results clearly show that in the case DABCO/I1 the XB adduct is practically the only one present in solution, whereas for the other pairs a certain amount of non-XB adduct is present. Combining DFT and HOESY results, the amount of non-XB adducts can be roughly quantified under our experimental conditions as 4 % for DABCO/I2, between 10 and 20 % for Me3 Py/I1 and Me3 Py/I2, and 44 % for DABCO/Br.

19.
Eur J Med Chem ; 65: 448-55, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23748153

RESUMO

Bisphosphonates (BPs) are key drugs for the treatment of bone resorption diseases like osteoporosis, Paget's disease and some forms of tumors. Recent findings underlined the importance of lipophilic N-containing BPs to ensure high biological activity. Herein we present some unprecedented results concerning the low toxicity and good anti-osteoclast activity of low molecular weight hydrophilic S-containing BPs. A series of S and N-containing BPs bearing aromatic and aliphatic substitution were prepared through Michael addition reaction between vinylidenebisphosphonate tetraethyl ester and the proper nucleophile under basic catalysis. S-containing BPs showed a generally low toxicity, determined with the neutral-red assay using the L929 cell line, and, in particular for an aliphatic one, a good biological activity assessed on primary cultures of human osteoclasts.


Assuntos
Difosfonatos/farmacologia , Osteoclastos/efeitos dos fármacos , Enxofre/química , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Colágeno/antagonistas & inibidores , Colágeno/metabolismo , Difosfonatos/síntese química , Difosfonatos/química , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Peso Molecular , Osteoclastos/citologia , Relação Estrutura-Atividade
20.
Inorg Chem ; 52(10): 5729-41, 2013 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-23647564

RESUMO

The reactions of the nitrile complexes cis- and trans-[PtCl2(NCR)2] (R = Me, Et, CH2Ph, Ph) with an excess of ethanethiol, EtSH, in the presence of a catalytic amount of n-BuLi in tetrahydrofuran (THF), afforded in good yield the bis-imino thioether derivatives cis-[PtCl2{E-N(H)═C(SEt)R}2] (R = Me (1), Et (2), CH2Ph (3), Ph (4)) and trans-[PtCl2{E-N(H)═C(SEt)R}2] (R = Me (5), Et (6), CH2Ph (7), Ph (8)). The imino thioether ligands assumed the E configuration corresponding to a cis addition of the thiol to the nitrile triple bond. The spectroscopic properties of these complexes have been reported along with the molecular structures of 1, 2, and 7 as established by X-ray crystallography which indicated that these compounds exhibit square-planar coordination geometry around the platinum center. Four N-H···Cl intermolecular contacts (N-H···Cl ca. 2.5-2.7 Å) between each chlorine atom and the N-H proton of the imino thioether ligand gave rise to "dimers" Pt2Cl4L4 (L = imino thioether) formed by two PtCl2L2 units. The cytotoxic properties of these new platinum(II) complexes were evaluated against various human cancer cell lines. Among all derivatives, trans-[PtCl2{E-N(H)═C(SEt)CH2Ph}2] showed the greatest in vitro cytotoxic activity being able to decrease cancer cell viability roughly 3-fold more effectively than cisplatin.


Assuntos
Antineoplásicos/farmacologia , Iminas/química , Compostos Organoplatínicos/farmacologia , Sulfetos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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