Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443600

RESUMO

Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 µM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.


Assuntos
Apoptose/genética , Ácido Butírico/química , Neoplasias do Colo/patologia , Estresse do Retículo Endoplasmático/genética , Epigênese Genética/efeitos dos fármacos , Compostos de Trialquitina/química , Compostos de Trialquitina/farmacologia , Acetilação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos
2.
Int J Mol Sci ; 21(21)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143349

RESUMO

Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment.


Assuntos
Autofagia , Neoplasias do Colo/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Compostos de Trialquitina/farmacologia , Apoptose , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Fator 2 Relacionado a NF-E2/genética , Células Tumorais Cultivadas
3.
J Inorg Biochem ; 205: 110999, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31986423

RESUMO

Ferulic acid (FA) is a natural phenolic phytochemical that has low toxicity and exhibits therapeutic effects against various diseases, behaving as an antioxidant. FA also displays modest antitumor properties that have been reported at relatively high concentrations. With the aim of improving the anti-tumor efficacy of FA, we synthesized the novel compound tributyltin(IV) ferulate (TBT-F). The coordination environment at the tin center was investigated spectroscopically. Following synthesis, chemical characterization and computational analysis, we evaluated TBT-F effects in colon cancer cells. The results showed that TBT-F, at nanomolar range concentrations, was capable of reducing the viability of HCT116, HT-29 and Caco-2 colon cancer cells. On the other hand, FA was completely inefficacious at the same treatment conditions. Cell viability reduction induced by TBT-F was associated with G2/M cell cycle arrest, increase in membrane permeabilization and appearance of typical morphological signs. TBT-F-induced cell death seemed not to involve apoptotic or necroptotic markers whereas autophagic vacuoles appearance and increase in LC3-II and p62 autophagic proteins were observed after treatment with the compound. The autophagy inhibitor bafylomicin A1 markedly prevented the effect of TBT-F on colon cancer cells, thus indicating that autophagy is triggered as a cell death process. Taken together, our results strongly suggest that the novel ferulic derivative TBT-F is a promising therapeutic agent for colon cancer since it is capable of triggering autophagic (type-II) cell death that may be important in case of resistance to classic apoptosis.


Assuntos
Antineoplásicos , Morte Celular Autofágica/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Ácidos Cumáricos , Compostos de Trialquitina , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Células CACO-2 , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Células HCT116 , Células HT29 , Humanos , Compostos de Trialquitina/síntese química , Compostos de Trialquitina/química , Compostos de Trialquitina/farmacologia
4.
Cells ; 8(12)2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801187

RESUMO

Melanoma is the most aggressive and deadly form of skin cancer, which is largely due to its propensity to metastasize. Therefore, with the aim to inhibit the growth and the metastatic dissemination of melanoma cells and to provide a novel treatment option, we studied the effects of the melanoma treatment with two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, namely (Bu2Sn)2TPPS and (Bu3Sn)4TPPS. In particular, we showed that nanomolar concentrations of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of the full-length poly (ADP-ribose) polymerase (PARP-1), to induce the cell cycle arrest respectively at G2/M and G0/G1 through the inhibition of the Cyclin D1 expression and to inhibit cell colony formation. Nanomolar concentrations of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS are also sufficient to inhibit the melanoma cell migration and the expression of some adhesion receptors. Moreover, we report that (Bu2Sn)2TPPS and (Bu3Sn)4TPPS act downstream of BRAF, mainly bypassing its functions, but targeting the STAT3 signalling protein. Finally, these results suggest that (Bu2Sn)2TPPS and (Bu3Sn)4TPPS may be effective therapeutic strategies for their role in the inhibition of melanoma growth and migration.


Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Porfirinas/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Quinase 1 de Adesão Focal/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Estrutura Molecular , Porfirinas/química , Transdução de Sinais/efeitos dos fármacos
5.
Phys Chem Chem Phys ; 20(15): 10445-10449, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29616694

RESUMO

The emission of silicon nanocrystals (Si-NCs), synthesized by pulsed laser ablation in water, was investigated on varying the pH of the solution. These samples emit µs decaying orange photoluminescence (PL) associated with radiative recombination of quantum-confined excitons. Time-resolved spectra reveal that both the PL intensity and the lifetime increase by a factor of ∼20 when the pH decreases from 10 to 1 thus indicating that the emission quantum efficiency increases by inhibiting nonradiative decay rates. Infrared (IR) absorption and electron paramagnetic resonance (EPR) experiments allow addressing the origin of defects on which the excitons nonradiatively recombine. The linear correlation between the PL and the growth of SiH groups demonstrates that H+ ions passivate the nonradiative defects that are located in the interlayer between the Si-NC core and the amorphous SiO2 shell.

6.
J Inorg Biochem ; 163: 311-317, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27393277

RESUMO

The interaction of the diorgano- and triorganotin(IV) derivatives of meso-tetra-(4-sulfonatophenyl)porphine (Me2Sn)2TPPS, (Bu2Sn)2TPPS, (Me3Sn)4TPPS and (Bu3Sn)4TPPS to natural DNA was analysed (together with free meso-tetra-(4-sulfonatophenyl)porphine (TPPS4-) for comparison purposes). Particular attention was paid to (Bu3Sn)4TPPS, a species that shows significant cellular action. Preliminary tests were done on the solution properties of the organotin(IV) compounds (pKA and possible self-aggregation). Spectrophotometric and spectrofluorometric experiments showed that all the investigated organotin(IV) derivatives strongly interact with DNA, the binding energy depending on the dye steric hindrance. In all cases experimental data concur in indicating that external binding mode prevails. Interestingly, fluorescence quenching and viscosity experiments show that the Bu-containing species, and in particular (Bu3Sn)4TPPS, are able to noticeably alter the DNA conformation.


Assuntos
DNA/química , Conformação de Ácido Nucleico , Compostos Orgânicos de Estanho , Porfirinas , Células A549 , DNA/metabolismo , Humanos , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Porfirinas/síntese química , Porfirinas/química , Porfirinas/farmacologia
7.
Biomacromolecules ; 14(11): 3820-9, 2013 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-24102383

RESUMO

Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors by modulating the balance between the hydrophobic and hydrophilic chains at both CyD sides. This work aimed to design nanoassemblies based on nonionic and hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the porphyrin derivatives under simulated physiological conditions, a speciation was performed using complementary techniques. In aqueous solution (≤ 20 µM), (Bu3Sn)4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the low static anisotropy (ρ ≈ 0.02) with a negligible formation of porphyrin supramolecular aggregates. MALDI-TOF spectra indicate the presence of moieties (i.e., [(Bu3Sn)3TPPS](-)) that are derivatives of the monomeric species. Spectrofluorimetry coupled with potentiometric measurements primarily assesses the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4](4-) species under physiological conditions. Nanoassemblies of (Bu3Sn)4TPPS/SC6OH were prepared by dispersion of organic films in PBS at pH 7.4 and were investigated using a combination of spectroscopic and morphological techniques. The UV-vis and emission fluorescence spectra of the (Bu3Sn)4TPPS/SC6OH reveal shifts in the peculiar bands of the organotin(IV)-porphyrin derivative due to its interaction with the ACyD supramolecular assemblies in aqueous solution. The mean size was within the range of 100-120 nm. The ξ-potential was negative (-16 mV) for the (Bu3Sn)4TPPS/SC6OH nanoassemblies, with an entrapment efficiency of approximately 67%. The intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were evaluated via fluorescence microscopy on A375 human melanoma cells. The delivery of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases the internalization efficiency and cytotoxicity to induce apoptotic cell death and, at lower concentrations, changes the cellular morphology and prevents cell proliferation.


Assuntos
Antineoplásicos/farmacologia , Ciclodextrinas/química , Melanoma/tratamento farmacológico , Nanomedicina , Tensoativos/farmacologia , Compostos de Trialquitina/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclodextrinas/administração & dosagem , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Melanoma/patologia , Estrutura Molecular , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Tensoativos/administração & dosagem , Tensoativos/química , Compostos de Trialquitina/administração & dosagem , Compostos de Trialquitina/química , Células Tumorais Cultivadas
8.
J Inorg Biochem ; 125: 16-25, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23685346

RESUMO

Three new triorganotin(IV) complexes of valproic acid (vp1, Me3Sn-valproate; vp2, Bu3Sn-valproate; vp3, Ph3Sn-valproate) have been synthesized and investigated by spectroscopic and biological methods. An anionic, monodentate valproate ligand was observed, ester-like coordinating the tin atom on a tetra-coordinated, monomeric environment. The structures, though, can distort towards a penta-coordination, as a consequence of a long range O···Sn interaction. Crystallographic and NMR findings confirm this situation both in solid state and solution. Biological finding evidenced a clear cytotoxic action of the complexes in hepatocellular carcinoma cell cultures: one of the complexes induced an 80% cell viability reduction after 24h treatment in HepG2 cells. This effect was accompanied by the appearance of biochemical signs of apoptosis. In Chang liver cells, the same compound induced only modest effects, suggesting a potential use as anti-cancer drug. Preliminary evaluations on hyperacetylation state of histone H3 in tributyltin-valproate treated HepG2 cells showed an increase in Ac-H3 (histone H3 acetylated at lys-9 and lys-14), suggesting that the compound maintains the deacetylation inhibition activity of its ligand valproate.


Assuntos
Antineoplásicos/síntese química , Histonas/metabolismo , Compostos Orgânicos de Estanho/síntese química , Ácido Valproico/análogos & derivados , Ácido Valproico/química , Acetilação , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular , Células Cultivadas , Células Hep G2 , Histonas/química , Humanos , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Ácido Valproico/síntese química , Ácido Valproico/farmacologia
9.
Int J Oncol ; 38(3): 693-700, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21206968

RESUMO

In previous studies we have demonstrated that two derivatives of meso-Tetra(4-sulfonatophenyl)porphine (TPPS), (Bu2Sn)2TPPS and (Bu3Sn)4TPPS, cause apoptotic death of A375 melanoma cells and, at lower concentrations, arrest of cell proliferation. In the present study, we examined if the manganese metal inside the porphyrin cavity could improve the efficacy of this class of compounds. Thus, [meso-Tetra(4-sulfonatophenyl)porphine]Mn(III)Cl (=MnTPPS) derivatives, namely (Me2Sn)2MnTPPS, (Bu2Sn)2MnTPPS, (Me3Sn)4MnTPPS and (Bu3Sn)4MnTPPS, were tested on the A375 human melanoma cell line. A cytotoxicity assay showed that (Bu2Sn)2MnTPPS and (Bu3Sn)4MnTPPS were highly cytotoxic by inducing apoptosis in melanoma cells, as shown by DNA fragmentation analysis and by apoptotic nuclei fluorescence, and when used at lower concentrations, they affected only cellular proliferation. An arrest of cell proliferation was also observed with (Me3Sn)4MnTPPS, but at the highest concentrations used. Moreover, the lower concentration of (Bu3Sn)4MnTPPS induced a change in cell morphology, from a polygonal to an elongated and spindle-shaped phenotype, likewise to its cognate (Bu3Sn)4TPPS, previously tested. Western blotting analysis showed indeed that both tributyltin compounds, i.e. (Bu3Sn)4MnTPPS and (Bu3Sn)4TPPS, lowered levels of the major proteins involved in tumorigenesis: ß-catenin, c-myc and snail. We also demonstrated that all compounds entered the cells and localized in the nuclei. In conclusion, our results show that, in spite of the Mn(III) metal introduction, the butyl derivatives always have a higher efficacy than methyl derivatives, and the tributyltin compounds in particular have an interesting effect in vitro on A375 cell proliferation.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Melanoma/patologia , Metaloporfirinas/farmacologia , Neoplasias Cutâneas/patologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cloretos/química , Fragmentação do DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Porfirinas/química , Porfirinas/farmacologia
10.
J Inorg Biochem ; 104(7): 750-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20421134

RESUMO

Diorganotin(IV) complexes of N-acetyl-L-cysteine (H(2)NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, (1)H, (13)C and (119)Sn NMR spectroscopy. FTIR results suggested that in R(2)Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC(2-) behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From (119)Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R(2)Sn(IV) trigonal bipyramidal configuration. In DMSO-d(6) solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu(2)SnCl(2) and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu(2)SnCl(2), suggesting that the binding with NAC(2-) modulates the marked cytotoxic activity exerted by Bu(2)SnCl(2). Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.


Assuntos
Acetilcisteína/química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Compostos Orgânicos de Estanho/química , Antineoplásicos/síntese química , Sítios de Ligação , Linhagem Celular , Humanos , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/farmacologia , Análise Espectral
11.
Oncol Rep ; 21(3): 593-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19212616

RESUMO

Previously we showed apoptotic induction in A375 human melanoma cells using two complexes of the meso-tetra(4-sulfonatophenyl)porphinate (TPPS), (Bu2Sn)2TPPS and (Bu3Sn)4TPPS. To understand how these compounds activate apoptosis in melanoma cells we studied MAPKs and the (Bu2Sn)2TPPS and (Bu3Sn)4TPPS cellular uptake. Western blotting experiments showed activated protein kinases ERK 1/2, JNK and p38 in 10 microM (Bu2Sn)2TPPS- and 1 microM (Bu3Sn)4TPPS-treated melanoma cells, which suggests that the three MAP kinases are involved in the apoptotic death of A375-treated cells. By taking advantage of the porphyrin fluorescence, we found a fast concentration of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS in the nucleus and in the nucleoli compared to TPPS. A significantly reduced growth of A375 human melanoma cells was also observed after only 48 h treatment by using 500 nM of (Bu2Sn)2TPPS or 80 nM of (Bu3Sn)4TPPS. A strong slowdown of cell growth and loss of cell-cell interactions were visible by in vitro wound repair assay.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Melanoma/metabolismo , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Compostos Orgânicos de Estanho/farmacologia , Porfirinas/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Humanos , Microscopia de Fluorescência por Excitação Multifotônica , Proteínas Quinases Ativadas por Mitógeno/metabolismo
12.
Cancer Lett ; 238(2): 284-94, 2006 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-16140459

RESUMO

The cytotoxic effect of several diorganotin(IV) and triorganotin(IV)-meso-tetra(4-sulfonatophenyl)porphine derivatives was tested and only the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS showed cytotoxicity on A375 human melanoma cells. To examine the pathway of (Bu(2)Sn)(2)TPPS or (Bu(3)Sn)(4)TPPS induced A375 cell death, DNA fragmentation analysis, Annexin V binding and PI uptake as well as caspases activation analysis by Western blot were carried out. A375 cells treated exhibited several typical characteristics of apoptosis. Both the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS compounds activate caspase-8 and caspase-9 leading to caspase-3 activation. Thus, we propose that these two porphirin derivatives lead to the apoptosis of human melanoma cells via both death receptor-mediated and mitochondrial apoptotic pathways.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Melanoma/tratamento farmacológico , Compostos Orgânicos de Estanho/farmacologia , Porfirinas/farmacologia , Caspases/fisiologia , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Citometria de Fluxo , Humanos , Melanoma/patologia , Microscopia de Fluorescência
13.
J Inorg Biochem ; 99(6): 1294-305, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15917083

RESUMO

Four new organotin(IV) chlorin derivatives, [chlorin=chlorin-e(6)=21H,23H-porphine-2-propanoic acid, 18-carboxy-20-(carboxymethyl)-8-ethenyl-13-ethyl-2,3-di-hydro-3,7,12,17-tetramethyl-(2S-trans)-], with formula (R(2)Sn)(3)(chlorin)(2).2H(2)O (R=Me, n-Bu) and (R(3)Sn)(3)chlorin.2H(2)O (R=Me, Ph) have been synthesized. The solid state and solution phase structures have been investigated by FT-IR, (119)Sn Mössbauer, (1)H and (13)C NMR spectroscopy. In the solid state, (R(2)Sn)(3)(chlorin)(2).2H(2)O complexes contain six coordinated Sn(IV), in a skew trapezoidal environment by forming trans-R(2)SnO(4) polymeric units. As far as (R(3)Sn)(3)chlorin.2H(2)O complexes are concerned, Sn(IV) is five coordinated in a polymeric (oligomeric) trigonal bipyramidal environment and eq-R(3)SnO(2) units, in the solid state. In saturated solutions, a polymeric structure comparable to the solid phase, with carboxylate groups of the ligand behaving in monoanionic bidentate fashion bridging Sn(IV) atoms, was detected for the (Me(3)Sn)(3)chlorin.2H(2)O complex, while in more diluted ones a tetrahedral configuration for the trimethyltin(IV) moieties was observed. Cytotoxic activity of the novel organotin(IV) chlorin was investigated in order to assay the effect on sea urchin embryonic development. The results obtained demonstrated that (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O and (Ph(3)Sn)(3)chlorin.2H(2)O exerted the antimitotic effect on the early stages of sea urchin development. In addition, the cytotoxic effect exerted by (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O appeared with necrosis of the blastomeres, which were clearly destroyed. After treatment with (Ph(3)Sn)(3)chlorin.2H(2)O, a programmed cell death was triggered, as shown by light microscope observations through morphological assays. The apoptotic events in 2-cell stage embryos revealed: (i) DNA fragmentation, with the TUNEL reaction (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling); (ii) phosphatidylserine translocation in the membrane, with Annexin-V assay and (iii) cytoplasm blebbing, with the TUNEL reaction. The results demonstrated that the novel compound (Ph(3)Sn)(3)chlorin.2H(2)O was the most toxic derivative, by exerting antimitotic effect very early and by triggering apoptosis in the 2-cell stage of sea urchin embryonic development.


Assuntos
Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/toxicidade , Paracentrotus/efeitos dos fármacos , Paracentrotus/embriologia , Porfirinas/síntese química , Porfirinas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Blastômeros/citologia , Blastômeros/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Orgânicos de Estanho/química , Paracentrotus/citologia , Porfirinas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Mossbauer
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...