RESUMO
Organotin(IV) and iridium(III) complexes have shown good application potential in the field of anticancer; however, the aggregation-caused quenching (ACQ) effect induced by high concentration or dose has limited the research on their targeting and anticancer mechanism. Then, a series of aggregation-induced emission (AIE)-activated butyltin(IV)-iridium(III) imidazole-phenanthroline complexes were prepared in this study. Complexes exhibited significant fluorescence improvement in the aggregated state because of the restricted intramolecular rotation (RIR), accompanied by an absolute fluorescence quantum yield of up to 29.2% (IrSn9). Complexes demonstrated potential in vitro antiproliferative and antimigration activity against A549 cells, following a lysosomal-mitochondrial apoptotic pathway. Nude mouse models further confirmed that complexes had favorable in vivo antitumor and antimigration activity in comparison to cisplatin. Therefore, butyltin(IV)-iridium(III) imidazole-phenanthroline complexes possess the potential as potential substitutes for platinum-based drugs.
Assuntos
Antineoplásicos , Proliferação de Células , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Imidazóis , Irídio , Fenantrolinas , Fenantrolinas/química , Fenantrolinas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Animais , Camundongos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Proliferação de Células/efeitos dos fármacos , Imidazóis/química , Imidazóis/farmacologia , Irídio/química , Irídio/farmacologia , Camundongos Nus , Apoptose/efeitos dos fármacos , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/síntese química , Estrutura Molecular , Células A549RESUMO
Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted methodology. All compounds were characterized by ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), LRMS (Low-Resolution Mass Spectrometry), and solution NMR (1H, 13C, 119Sn Nuclear Magnetic Resonance) spectroscopies. Complexes Bu2Sn(Lys) (1), Ph2Sn(Lys) (2), Bu2Sn(Orn) (3), and Ph2Sn (Glu-OMe) (6a) were crystallized, and the structures were established by single-crystal X-ray diffraction analysis. Diffraction results evidenced that complexes 1 to 3 were five-coordinated mononuclear species while the phenyl substituted derivative Ph2Sn (Glu-OMe) (6a) forms a polymeric network via Sn-O-Sn bridging whereby the tin atom is six-coordinated. In turn, 119Sn NMR results revealed that all tin complexes exist as mononuclear penta-coordinated species in solution. The tin derivatives were screened for ADME (Adsorption, Distribution, Metabolism, and Excretion) properties via the freely available tools SWISS ADME, and the results were analyzed hereafter. The antiproliferative activity of the complexes was tested against three human cancer cell lines: colorectal adenocarcinoma HT-29, breast adenocarcinoma MDA-MB-231, and chondrosarcoma SW-1353 using a non-tumoral cell line of human osteoblast as control, demonstrating selective inhibitory activities against cancer cells. Hence, these compounds could be a promising alternative to classical chemotherapy agents.
Assuntos
Aminoácidos , Antineoplásicos , Compostos Orgânicos de Estanho , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/síntese química , Aminoácidos/química , Aminoácidos/síntese química , Linhagem Celular Tumoral , Cristalografia por Raios X , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/químicaRESUMO
Three distinctive end group-containing organotin (IV) carboxylates complexes (YDCOOSn, CLCOOSn and BZCOOSn) were designed and synthesized. Together with theoretical calculations, a thorough examination was carried out to investigate the photophysical properties of these compounds. The cytotoxicity of the synthesized compounds was tested using normal cell line GES-1 and was assessed against four cancer cell lines (A549, Hela, H1299 and HepG2). The outcomes of the experiments demonstrated that these complexes had superior selectivity than cisplatin towards cancerous cells, particularly in the A549 cell line. BZCOOSn was selected as a candidate compound for additional research because it exhibited the lowest IC50 value and the most impressive inducing effect on cell death and G2/M phase arrest. Increased caspase-3 and -9 enzyme activity, a decline in mitochondrial membrane potential (MMP), characteristic nuclear apoptotic morphology, and an accumulation of intracellular reactive oxygen species (ROS) were seen in A549 exposed to BZCOOSn. These findings demonstrated that BZCOOSn exhibited strong cytotoxicity by triggering cell death in A549 via the mitochondrial route. Furthermore, using the scratch wound healing assay, it was discovered that BZCOOSn reduced the migration of A549 cancerous cells. These data all pointed to BZCOOSn as a possible candidate for more research and development as a chemotherapeutic drug.
Assuntos
Antineoplásicos , Apoptose , Potencial da Membrana Mitocondrial , Compostos Orgânicos de Estanho , Espécies Reativas de Oxigênio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/síntese química , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células A549 , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Linhagem Celular Tumoral , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Movimento Celular/efeitos dos fármacos , Células HeLaRESUMO
Many diorganotin complexes with various alkyl groups exhibit excellent in vitro anticancer activity. However, most diorganotin is the same alkyl group, and the asymmetric alkyl R group has been rarely reported. Hence, in this paper, twenty butylphenyl mixed dialkyltin arylformylhydrazone complexes have been synthesized by microwave "one-pot" reaction with arylformylhydrazine, substituted α-keto acid or its sodium salt and butylphenyltin dichloride. The crystal structures of nine complexes were determined, indicating that the complexes C1, C2, C11, C12, and C16 â¼ C19 possessed a central symmetric structure of a dinuclear Sn2O2 tetrahedral ring; while the complex C9 is a trinuclear tin-oxygen cluster with a 6-membered ring encased in a 12-membered macrocyclic structure. The inhibiting activity of complexes was tested against the human cell lines NCI-H460, MCF-7, HepG2, Huh-7 and HL-7702. Complex C2 demonstrated the optimal inhibitory effect on HepG2 cells, with an IC50 value of 0.82 ± 0.03 µM. Cellular biology experiments revealed that complex C2 could induce apoptosis and G2/M phase cell cycle arrest in HepG2 and Huh-7 cells. The complex also caused the collapse of the mitochondrial membrane potential and increased intracellular reactive oxygen species in HepG2 and Huh-7 cells. Western blot analysis further clarified that complex C2 could induce cell apoptosis through the mitochondrial pathway along with the release of reactive oxygen species.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Hidrazonas , Compostos Orgânicos de Estanho , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/síntese química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. METHODS: The two ONBDC derivatives - ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) - were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. RESULTS: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 µM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 µM). CONCLUSION: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.
Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Orgânicos de Estanho , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Células A549 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Tiocarbamatos/química , Tiocarbamatos/farmacologia , Tiocarbamatos/síntese química , Desenvolvimento de MedicamentosRESUMO
Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1- = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2- = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3- = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.
Assuntos
Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Orgânicos de Estanho , Quinolonas , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Animais , Camundongos , Quinolonas/química , Quinolonas/farmacologia , Quinolonas/síntese química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Estrutura Molecular , Relação Estrutura-Atividade , Sobrevivência Celular/efeitos dos fármacosRESUMO
Two novel triphenyltin(IV) compounds, [Ph3SnL1] (L1â¯=â¯2-(5-(4-fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph3SnL2] (L2â¯=â¯2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (1H and 13C) NMR spectroscopy, mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV) compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), and HepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. The IC50 values are found to be in the range from 0.11 to 0.50⯵M. Compound 1 exhibits the highest activity toward PC-3 cells (IC50â¯=â¯0.115⯱â¯0.009⯵M; CV assay). The tin and platinum uptake in PC-3 cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higher activity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100 times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometry analysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.
Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias/tratamento farmacológico , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/farmacologia , Propionatos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Neoplasias/metabolismo , Neoplasias/patologia , Óxido Nítrico/metabolismo , Compostos Orgânicos de Estanho/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tiazolidinas/químicaRESUMO
D-Glycero-D-mannno-heptose 1ß, 7-bisphosphate (HBPß) is an important intermediate for constructing the core structure of Gram-negative bacterial lipopolysaccharides and was reported as a pathogen-associated molecular pattern (PAMP) that regulates immune responses. HBPß with 3-O-amyl amine linker and its monophosphate derivative D-glycero-D-mannno-heptose 7-phosphate (HP) with 1α-amyl amine linker have been synthesized as candidates for immunity study of HBPß. The O3-amyl amine linker of heptose was installed by dibutyltin oxide-mediated regioselective alkylation under fine-tuned protecting condition. The stereoselective installation of 1ß-phosphate ester was achieved by NIS-mediated phosphorylation at low temperature. The strategy for installation of 3-O-amyl amine linker onto HBP derivative can be expanded to the syntheses of other conjugation-ready carbohydrates bearing anomeric phosphoester.
Assuntos
Aminas/síntese química , Bactérias Gram-Negativas/química , Heptoses/síntese química , Lipopolissacarídeos/química , Compostos Orgânicos de Estanho/síntese químicaRESUMO
Starting out from dipotassium 1,5-oligosiloxanylene diide 2, a 3,7,10-trioxa-octasilabicyclo[3.3.3]undecane was prepared, which represents the third known example of this cage structure type. Reaction of 1,3-dichlorotetramethyldisiloxane with 1,1'-bis[bis(trimethylsilyl)potassiosilyl]ferrocene gave a ferrocenophane with a disiloxane containg bridge. The compound can be further derivatized by conversion into a 1,5-oligosilanyl diide. Reacting 1,5-oligosiloxanylene diide 2 with SnCl2 or GeCl2·dioxane in the presence of PMe3 gave cyclic disilylated tetrylene PMe3 adducts. Release of the base-free stannylene led to a dimerization process which gave a bicyclic distannene as the final product. Abstraction of the PMe3 from the cyclic disilylated germylene PMe3 adduct with B(C6F5)3 caused oxidative addition of the germylene into a para-C-F bond of Me3P·B(C6F5)3.
Assuntos
Complexos de Coordenação/síntese química , Compostos Ferrosos/síntese química , Metalocenos/síntese química , Compostos Orgânicos de Estanho/síntese química , Silanos/química , Siloxanas/química , Complexos de Coordenação/química , Ciclização , Conformação MolecularRESUMO
Six novel organotin phosphonate complexes, [(Me3Sn)4(HL1)4]n1, [(Me3Sn)2(HL2)2]n2, [(Me3Sn)2L3(H2O)]n3, [(Ph3Sn)(HL1)]64, [(Ph3Sn)2L2]n5 and [(Ph3Sn)2L3]66, derived from phosphonic acid ligands [NaHL1 = 1-C10H7OPO2(OH)Na, H2L2 = 1-C10H7PO(OH)2, H2L3 = 2-C10H7PO(OH)2], have been synthesized and characterized by elemental analysis, FT-IR, NMR (1H, 13C, 31P and 119Sn) spectroscopy and X-ray crystallography. The structural analysis reveals that complexes 1 and 5 display 1D infinite zig-zag chain structures, and complex 2 shows 1D right-handed helical chain structure, while complex 3 displays 1D left-handed helical chain structure. Complexes 4 and 6 are 24-membered macrocyclic rings interconnected by P, O and Sn atoms. Additionally, the molecules of complexes 1 and 3 are further linked through intermolecular π···π and O-H···O interaction into supramolecular structures, respectively. Furthermore, we preliminarily estimated in vitro cytostatic activity of complexes 1-6 against the human cervix tumor cells (HeLa), human hepatocellular carcinoma cells (HepG-2) and human normal breast cells (HBL-100). Importantly, the anti-proliferative properties and possible pathway of complex 6 are investigated, and the results demonstrate that complex 6 could induce apoptotic cell death via an overload of intracellular reactive oxygen species (ROS) levels and the dysfunctional depolarization of mitochondrial membranes.
Assuntos
Citostáticos/química , Citostáticos/farmacologia , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Ácidos Fosforosos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Citostáticos/síntese química , Feminino , Células HeLa , Humanos , Ligantes , Neoplasias Hepáticas/patologia , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Ácidos Fosforosos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Estanho/química , Neoplasias do Colo do Útero/patologiaRESUMO
In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO- ligands belonging to adjacent chains were also detected that resemble the "base-pairing" assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.
Assuntos
Apoptose/efeitos dos fármacos , Citotoxinas/farmacologia , Regulação Neoplásica da Expressão Gênica , Compostos Orgânicos de Estanho/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Apoptose/genética , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citotoxinas/síntese química , Desenho de Fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Células HCT116 , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Compostos Orgânicos de Estanho/síntese química , Pirimidinas/síntese química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Visual detection of the methylglyoxal (MGO) level in the brain is critical for understanding its role in the onset and progression of AD. Herein, we disclosed a NIR fluorescent probe, DBTPP, for detecting MGO by utilizing a thiadiazole-fused o-phenylenediamine moiety as a MGO-specific sensing unit. DBTPP exhibits a series of distinct advantages, such as NIR emission, high selectivity and sensitivity, excellent acid-stability, and a huge off-on ratio. The probe could accurately monitor both exogenous and endogenous MGO variations in SH-SY5Y cells. Besides, it was able to image the endogenous MGO in a transgenic AD mouse model successfully, suggesting the great potential of MGO as a biomarker for early AD diagnosis.
Assuntos
Doença de Alzheimer/metabolismo , Corantes Fluorescentes/química , Ácido Gálico/análogos & derivados , Compostos Orgânicos de Estanho/química , Fenilenodiaminas/química , Aldeído Pirúvico/análise , Tiadiazóis/química , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Ácido Gálico/síntese química , Ácido Gálico/química , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Compostos Orgânicos de Estanho/síntese química , Fenilenodiaminas/síntese química , Presenilina-1/genética , Aldeído Pirúvico/metabolismo , Tiadiazóis/síntese químicaRESUMO
Eight organotin(IV) complexes (C1-C8) have been synthesized and characterized by elemental analysis, fourier transform infrared spectroscopy (FT-IR), multinuclear nuclear magnetic resonance (1H, 13C and 119Sn NMR), high resolution mass spectroscopy (HRMS) and single crystal X-ray structural analysis. Crystallographic data show that C1 was a tetranuclear 16-membered macrocycle complex, C2-C4 and C7 were centrosymmetric dimer distannoxane and there was a Sn2O2 four-membered ring in the middle of the molecule, respectively, C5 and C6 are monoorganotin complexes due to the dehydroalkylation effect during the reaction, while C8 forms a one-dimensional chain structure. The cytotoxicity of all complexes were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays against three human tumor cell lines NCI-H460, MCF-7 and HepG2. The dibutyltin complex C2 has been shown to be more potent antitumor agents than other complexes and carboplatin. Cell apoptosis study of C2 with the high activity on HepG2 and MCF-7 cancer cell lines was investigated by flow cytometry, it was shown that the antitumor activity of C2 was related to apoptosis, but it has different cell cycle arrest characteristics from platinum compounds, and the proliferation was inhibited by blocking cells in S phase. The DNA binding activity of the C2 was studied by UV-visible absorption spectrometry, fluorescence competitive, viscosity measurements and gel electrophoresis, results shown C2 can be well embedded in the double helix of DNA and cleave DNA.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA de Neoplasias/efeitos dos fármacos , Glioxilatos/farmacologia , Ácidos Mandélicos/farmacologia , Compostos Orgânicos de Estanho/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioxilatos/síntese química , Glioxilatos/química , Humanos , Ácidos Mandélicos/síntese química , Ácidos Mandélicos/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Relação Estrutura-AtividadeRESUMO
Poly(vinyl chloride) (PVC), a polymer widely used in common household and industrial materials, undergoes photodegradation upon ultraviolet irradiation, leading to undesirable physicochemical properties and a reduced lifetime. In this study, four telmisartan organotin(IV) compounds were tested as photostabilizers against photodegradation. PVC films (40-µm thickness) containing these compounds (0.5 wt%) were irradiated with ultraviolet light at room temperature for up to 300 h. Changes in various polymeric parameters, including the growth of hydroxyl, carbonyl, and alkene functional groups, weight loss, reduction in molecular weight, and appearance of surface irregularities, were investigated to test the efficiency of the photostabilizers. The changes were more noticeable in the blank PVC film than in the films containing the telmisartan organotin(IV) compounds. These results reflect that these compounds effectively inhibit the photodegradation of PVC, possibly by acting as hydrogen chloride and radical scavengers, peroxide decomposers, and primary photostabilizers. The synthesized organotin(IV) complexes could be used as PVC additives to enhance photostability.
Assuntos
Compostos Orgânicos de Estanho/síntese química , Cloreto de Polivinila/química , Telmisartan/química , Ácido Clorídrico/química , Estrutura Molecular , Peso Molecular , Compostos Orgânicos de Estanho/química , Fotólise , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl- and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no interaction and by UV-vis titration exhibiting moderate interaction by intercalation. Complexes having n-butyl substituents were more potent and cytotoxic against human leukemia, breast and cervical cancer cell lines than other organotin(IV) complexes tested. Unfortunately, some of these compounds showed similar cytotoxicity in a non-cancerous cell line. We may conclude that cytotoxic activity was dependent on the nature (lipophilicity and size, according to the structure-activity relationship studies) and substitution pattern on the different structures. These results may aid in the rational design of metallodrugs, expanding the scope of organotin complexes in formulating new metal based drugs with dibutyl moieties.
Assuntos
Antineoplásicos/farmacologia , Compostos Orgânicos de Estanho/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Relação Estrutura-AtividadeRESUMO
Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear (¹H, 13C, 119Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph2SnCl2 or Me2SnCl2 with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R2Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me2Sn(S2MoVa), Me2Sn(S4MoVa) and Me2Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C2NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.
Assuntos
Benzaldeídos/síntese química , Benzaldeídos/farmacologia , Simulação por Computador , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Benzaldeídos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalografia por Raios X , DNA/metabolismo , Humanos , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Compostos Orgânicos de Estanho/química , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/químicaRESUMO
Compared to organotin (IV) compounds with biochemical activity, two-photon absorption (2PA) organotin (IV) complexes for targeting nuclear with anticancer activities are rarely reported. Here, two novel 2PA organotin (IV) cyano carboxylate complexes (C1Sn-1, C1Sn-2) are synthesized and characterized. The two-photon absorption cross section values (δ) in the near-infrared region are significantly enhanced for C1Sn-2 compared to C1Sn-1, thus developing for targeting nuclear by two-photon fluorescence microscopy (2PFM). C1Sn-2 could specifically target nuclear DNA in vitro. The mechanism demonstrated that there are abundant hydrogen bond interactions between hydroxy group of C1Sn-2 and DNA. The animal mode studies are first proposed that C1Sn-2 displayed a certain anti-cancer efficiency with non-significant toxicity.
Assuntos
Núcleo Celular/metabolismo , DNA de Neoplasias/metabolismo , Neoplasias Experimentais/metabolismo , Compostos Orgânicos de Estanho , Animais , Núcleo Celular/patologia , Camundongos , Microscopia de Fluorescência , Neoplasias Experimentais/patologia , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Relação Estrutura-AtividadeRESUMO
A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand. All new complexes were fully characterized by spectroscopic techniques, consisting of IR, MS and NMR (1H, 13C and 119Sn). The in vitro cytotoxicity tests demonstrated that the organotin complexes produced a greater inhibition, versus cisplatin (the positive control), of the growth of six human cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and SKLU-1 (non-small cell lung). The potency of this cytotoxic activity depended on the nature of the substituent bonded to the aromatic ring. All complexes exhibited excellent IC50 values. The test compounds were also screened in vitro for their antifungal effect against Candida glabrata and Candida albicans, showing minimum inhibitory concentration (MIC) values lower than those obtained for fluconazole. A brine shrimp bioassay was performed to examine the toxic properties. Molecular docking studies demonstrated that the organotin(IV) complexes bind at the active site of topoisomerase I in a similar manner to topotecan, sharing affinity for certain amino acid side chains (Ile535, Arg364 and Asp533), as well as for similar DNA regions (DA113, DC112 and DT10).
Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Artemia/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Compostos Orgânicos de Estanho/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Orgânicos de Estanho/síntese química , Compostos Orgânicos de Estanho/química , Relação Estrutura-AtividadeRESUMO
The total phenolic content, flavonoid content, in vitro xanthine oxidase (XOD) inhibitory activity and antioxidant activity (AA) of Eucommia ulmoides Oliver leaf extracts were investigated. The AA investigations included 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ß-carotene/linoleic acid bleaching assay and oxygen radical absorbance capacity (ORAC) test. The ethyl acetate fraction (EE) showed the highest AA and xanthine oxidase inhibitory activity. Whilst the lowest 50% inhibition (IC50) value of this fraction for DPPH free radical scavenging was 0.045mg/mL, its highest ORAC value was 10.57 µmol TE/mg. The highest inhibition rate against linoleic acid oxidation observed was 69.41%, and the lowest IC50 value for xanthine oxidase activity inhibition was 2.47mg/mL. These results show that E. ulmoides leaf extract is a promising source of natural antioxidants because it contains high contents of bioactive compounds, including chlorogenic acid, rutin, hyperin and astragalin, as detected by high-performance liquid chromatography coupled to HPLC-DAD-ESI-MS.
Assuntos
Anti-Infecciosos/síntese química , Inibidores Enzimáticos/síntese química , Compostos Orgânicos de Estanho/síntese química , Urease/antagonistas & inibidores , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Bases de Schiff/químicaRESUMO
We have compared the anti-proliferative activity in vitro, of R2SnGala (1-3) [Râ¯=â¯Me, n-Bu, Ph] and novel R3SnGala (4, 5) [Râ¯=â¯Me, n-Bu] with D-(+)-Galacturonic acid [HGala; Galaq-, qâ¯=â¯(2) and (1) for R2SnGala and R3SnGala, respectively] compounds, towards human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by 1H, 13C and 119Sn NMR, that showed that HGala acts as monoanionic moiety and evidenced the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry, respectively. The cytotoxicity of the compounds, in the micro-submicromolar range, changed in the order of the organotin(IV) moieties, according to 5â¯>â¯3â¯>â¯2, while 1 and 4, containing MenSn(IV) (nâ¯=â¯2,3) moieties, were ineffective. Compound 5 showed peculiar cytotoxic effects. It did not cause time dependent inhibition of cell growth nor accumulated into the cells. Cell death induced by the active 2, 3, and 5, was shown to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and the loss of mitochondrial potential. All the cytotoxic compounds induced an accumulation of cells in the subG0/G1phase, while only 2 and 3 perturbed the cell cycle confining viable cells in G0/G1phase. Finally, none of the compounds investigated affected the viability of normal intestinal or liver cells, indicating selectivity towards tumor cells.