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
Organotins have been widely used in various industrial applications. This study investigated the structure-activity relationship as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD). Human KGN cell, pig, and rat testis microsomes were utilized to assess the inhibitory effects of 18 organotins on the conversion of pregnenolone to progesterone. Among them, diphenyltin, triethyltin, and triphenyltin exhibited significant inhibitory activity against human 3ß-HSD2 with IC50 values of 114.79, 106.98, and 5.40 µM, respectively. For pig 3ß-HSD, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin demonstrated inhibitory effects with IC50 values of 172.00, 100.19, 87.00, 5.75, and 1.65 µM, respectively. Similarly, for rat 3ß-HSD1, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin displayed inhibitory activity with IC50 values of 81.35, 43.56, 55.55, 4.09, and 0.035 µM, respectively. They were mixed inhibitors of pig and rat 3ß-HSD, while triphenyltin was identified as a competitive inhibitor of human 3ß-HSD2. The mechanism underlying the inhibition of organotins on 3ß-HSD was explored, revealing that they may disrupt the enzyme activity by binding to cysteine residues in the catalytic sites. This proposition was supported by the observation that the addition of dithiothreitol reversed the inhibition caused by all organotins except for triethyltin, which was partially reversed. In conclusion, this study provides valuable insights into the structure-activity relationship of organotins as inhibitors of human, pig, and rat gonadal 3ß-HSD. The mechanistic investigation suggests that these compounds likely exert their inhibitory effects through binding to cysteine residues in the catalytic sites.
Assuntos
Inibidores Enzimáticos , Compostos Orgânicos de Estanho , Testículo , Animais , Humanos , Relação Estrutura-Atividade , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Ratos , Masculino , Testículo/enzimologia , Testículo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Suínos , 3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 3-Hidroxiesteroide Desidrogenases/metabolismo , Simulação de Acoplamento Molecular , Progesterona/farmacologia , Progesterona/metabolismo , Microssomos/enzimologia , Microssomos/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
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
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
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
A series of novel dibutyltin complexes based on salen-like ligands (S01-S03) were synthesized and characterized using ultraviolet-visible spectraï¼infrared spectra, 1H, 13C, and 119Sn nuclear magnetic resonance, high-resolution mass spectrometry, X-ray crystallography, and thermogravimetric analysis. Complex S03 had excellent anticancer activity in vitro (IC50 = 1.5 ± 0.2 µM in CAL-27 cell lines), which highly activated ROS expression levels and induced apoptosis and cell cycle arrest at the G2/M phase. Interestingly, complex S03 induced cancer cell death through multiple mechanisms (mitochondrial pathway, ER-stress pathway, and DNA damage pathway). This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs in the future, and compounds with multiple anticancer mechanisms may be a new strategy for delaying or overcoming drug resistance to chemotherapy and target therapy.
Assuntos
Antineoplásicos , Complexos de Coordenação , Compostos Orgânicos de Estanho , Compostos Orgânicos de Estanho/química , Antineoplásicos/química , Etilenodiaminas/farmacologia , Complexos de Coordenação/química , Linhagem Celular Tumoral , Apoptose , LigantesRESUMO
Organotin (IV) dithiocarbamate has recently received attention as a therapeutic agent among organotin (IV) compounds. The individual properties of the organotin (IV) and dithiocarbamate moieties in the hybrid complex form a synergy of action that stimulates increased biological activity. Organotin (IV) components have been shown to play a crucial role in cytotoxicity. The biological effects of organotin compounds are believed to be influenced by the number of Sn-C bonds and the number and nature of alkyl or aryl substituents within the organotin structure. Ligands target and react with molecules while preventing unwanted changes in the biomolecules. Organotin (IV) dithiocarbamate compounds have also been shown to have a broad range of cellular, biochemical, and molecular effects, with their toxicity largely determined by their structure. Continuing the investigation of the cytotoxicity of organotin (IV) dithiocarbamates, this mini-review delves into the appropriate method for synthesis and discusses the elemental and spectroscopic analyses and potential cytotoxic effects of these compounds from articles published since 2010.
Assuntos
Antineoplásicos , Compostos Orgânicos de Estanho , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/químicaRESUMO
In the last few years, tin(IV) complexes have emerged as very attractive candidates in the field of molecular imaging due to their unique photophysical properties. Despite the few reviews published to date covering the chemistry of organotin and tin complexes and their cytotoxic potential, there are no reviews devoted to their live cell imaging properties. Therefore, this feature article summarizes the discussion of the fundamental photophysical properties of fluorescent tin metal complexes focusing on their recent advances in "biomedical molecular imaging". A debate on the design of tin complexes as cellular imaging agents relating to their chemical, electronic and photophysical properties is enclosed. This paper also discusses the imaging applications of tin complexes in cells, tissues, and organisms via confocal and multiphoton imaging for sensing mechanisms in cellular media, bioimaging, and therapeutic labeling. In addition, it explores and explains the current challenges and prospects associated with these tin complexes as emerging luminescent cellular agents for potential clinical use.
Assuntos
Complexos de Coordenação , Substâncias Luminescentes , Compostos Orgânicos de Estanho , Estanho , Complexos de Coordenação/toxicidade , Complexos de Coordenação/química , Substâncias Luminescentes/química , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Corantes , Imagem MolecularRESUMO
A number of novel di- and triorganotin(IV) complexes 1-5 (Ph2SnL1, Ph2SnL2, Et2SnL2, Ph3SnL3, Ph3SnL4) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds 1-5 were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes 1 and 2 in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds 4 and 5 with free phenol or catechol fragments are more active in these tests than complexes 1-3 with tridentate O,N,S-coordinated ligands. The effect of compounds 1-5 on the promoted oxidative damage of the DNA by 2,2'-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes 4 and 5 were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds 1-3. The antiproliferative activity of compounds 1-5 was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC50 are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.
Assuntos
Complexos de Coordenação , Compostos Orgânicos de Estanho , Ratos , Animais , Antioxidantes/farmacologia , Fenol , Bases de Schiff/química , Ratos Wistar , Compostos Orgânicos de Estanho/química , Fenóis/farmacologia , Catecóis/farmacologia , Complexos de Coordenação/química , LigantesRESUMO
A series of novel organotin(IV) complexes on the base of 2-(N-3',5'-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 µM for complex 2). Furthermore, compounds 1-5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.
Assuntos
Antineoplásicos , Compostos Orgânicos de Estanho , Humanos , Antioxidantes/farmacologia , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Bases de Schiff/farmacologia , Bases de Schiff/química , Cristalografia por Raios X , Antineoplásicos/farmacologiaRESUMO
BACKGROUND: Cancer cases have escalated by approximately 12% since 1900 and the incidence rate has increased faster for females than males. The discovery of cisplatin in 1965 paved the way for metal-based compounds as cancer therapeutics. Unfortunately, cisplatin and other platinum-based medicines cause severe side effects. Therefore, non-platinum metal complexes have been developed as alternate cancer drugs. Among non-platinum metal complexes, organotins are the most effective candidates in oncology due to their wide range of anticancer activities with relatively minimal toxicities towards healthy cells, better excretion from the body, and fewer side effects than platinum drugs. METHODS: Using DOI searching, advances made by organotin(IV) complexes coordinated with Sn-O, Sn-N and Sn-S as chemotherapeutic agents since 2018 are summarized in this article. Their chemical structure and in vitro antiproliferative activity in terms of IC50/EC50/LD50 are cumulated. RESULTS: As reflected in this perspective, organotin(IV) complexes are found to induce high cell death via apoptosis, and also several complexes demonstrated anticancer activity even higher than standard drugs. CONCLUSION: Undoubtedly, the organotin(IV) complexes could bring hope to morbidity and mortality of human beings caused by fast-spreading cancer worldwide and can play an important role in drug discovery.
Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Feminino , Humanos , Antineoplásicos/química , Cisplatino/uso terapêutico , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Citotoxinas , Neoplasias/tratamento farmacológico , Platina/química , Compostos Orgânicos de Estanho/químicaRESUMO
A novel polydentate chelating antioxidant ligand and series of organotin complexes on its base were synthesized and characterized by NMR 1H, 13C, 119Sn, IR spectroscopy, X-ray, and elemental analysis. Their antioxidant activity was evaluated in DPPH and NBT-tests, and as lipoxygenase inhibitory activity. It was shown that ligand alone is a radical scavenger, while introducing tin in the structure of the compound significantly decreases its activity. For the ligand alone the ability to strongly suppress the formation of advanced glycation end products (AGEs) was shown, which may be associated with the established antiradical activity. All synthesized compounds appeared to be moderate lipoxygenase inhibitors. The stability of compounds to hydrolysis under different pH was estimated. The ligand undergoes decomposition after about an hour, while organotin complexes on its base demonstrate vast stability, showing signs of decomposition only after 5 h of experimentation. Cytotoxicity of compounds was studied by standard MTT-test, which showed unorthodox results: the ligand itself demonstrated noticeable cytotoxicity while the introduction of organotin moiety either did not affect the toxicity levels or reduced them instead of increasing. Organotin complexes possess luminescence both as powders and DMSO solutions, its quantum yields reaching 67% in DMSO. The combination of luminescence with unique cytotoxic properties allows us to propose the synthesized compounds as perspective theranostic agents.
Assuntos
Antineoplásicos , Compostos Orgânicos de Estanho , Ligantes , Antioxidantes/farmacologia , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Antineoplásicos/farmacologia , Espectroscopia de Ressonância MagnéticaRESUMO
Five fluorescent ONO donor-based organotin(IV) complexes, [SnIV(L1-5)Ph2] (1-5), were synthesized by the one-pot reaction method and fully characterized spectroscopically including the single-crystal X-ray diffraction studies of 2-4. Detailed photophysical characterization of all compounds was performed. All the compounds exhibited high luminescent properties with a quantum yield of 17-53%. Additionally, the results of cellular permeability analysis suggest that they are lipophilic and easily absorbed by cells. Confocal microscopy was used to examine the live cell imaging capability of 1-5, and the results show that the compounds are mostly internalized in mitochondria and exhibit negligible cytotoxicity at imaging concentration. Also, 1-5 exhibited high photostability as compared to the commercial dye and can be used in long-term real-time tracking of cell organelles. Also, it is found that the probes (1-5) are highly tolerable during the changes in mitochondrial morphology. Thus, this kind of low-toxic organotin-based fluorescent probe can assist in imaging of mitochondria within living cells and tracking changes in their morphology.
Assuntos
Corantes Fluorescentes , Compostos Orgânicos de Estanho , Corantes Fluorescentes/farmacologia , Compostos Orgânicos de Estanho/farmacologia , Compostos Orgânicos de Estanho/química , Mitocôndrias , Cristalografia por Raios X , Microscopia ConfocalRESUMO
Over the last century, organotin compounds (OTCs) have sprawled over a vast spectrum of applications ranging from industrial to agricultural fields, interlacing with our surrounding environment and the ecosystem in an inseparable manner. The biocidal nature of OTCs, which has been exploited as the servient antifouling property, proved them to be pernicious eco-toxicants and a threat to the entire living system irrespective of the taxonomic hierarchy. Despite the recalcitrant nature of OTCs against chemical decontamination and photodegradation, nature has shown a providential method of their biodegradation by means of organotin-resistant microbes. Although the details of the microbial organotin biodegradation process remain nebulous, the cytochrome P450 (CYP450) family of enzymes has shown to possess the capability of OTC degradation. In this review, we discuss the deep-rooted toxicity problem of the organotin compounds on the biota and explore the plausible mechanistic plots of their enzymatic degradation, keeping the catalytic cycle of the CYP450 enzyme under the limelight. Leveraging the knowledge of CYP450 catalysis and the known organotin metabolites in nature, we attempt to cast transparency on the catalytic mechanism involved in organotin biodegradation, which remains largely elusive. Although several challenges have to be confronted for implementing the process of enzymatic degradation of OTCs in the real world, a sincere attempt will definitely be worth the ultimate greater good for averting the global toxicity problem related to organotin compounds.
Assuntos
Compostos Orgânicos de Estanho , Poluentes Químicos da Água , Ecossistema , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/toxicidade , Poluentes Químicos da Água/químicaRESUMO
Three di-organotin(IV) complexes have been synthesized by the reaction of Schiff base di-acylhydrazone ligands bis(5-chlorosalicylaldehyde) adipoylhydrazone and R2SnCl2 [R = Me (1), Ph (2), n-Bu (3)]. Structures of all complexes were characterized by 1H, 13C, 119Sn NMR, elemental analysis, IR and mass spectrometry. Experimental results showed that the symmetric diacylhydrazone ligands coordinate the tin atom in a hexadentate form, where the tin atom shows a penta-coordination, in a distorted triangular bipyramid geometry. Using MTT method, in vitro cytotoxicity of three complexes was determined against three cancer cell lines (A549, HeLa, HepG-2). Studies reveal that complex 3 showed the strongest cytotoxic activity among the three complexes, which may be correlated with the generation of intracellular reactive oxygen species. Uptake of complex 3 into cells and promotion of reactive oxygen species were visualized by confocal fluorescence imaging.
Assuntos
Compostos Orgânicos de Estanho , Bases de Schiff , Humanos , Ligantes , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Bases de Schiff/farmacologia , Estanho/químicaRESUMO
Recently inorganic-based metallodrugs provide an effective mechanism for the drugs on the choice of metal and its properties. Medicinal complex compounds provide an efficient platform for various pharmacological and therapeutic applications. Six new organotin and organosilicon complexes containing sulphur and nitrogen donor atoms were synthesised. These complexes of (E)-2-((4-methoxybenzylidene)amino)benzenethiol were characterized by elemental analyses, molecular weights, conductance measurements, infrared, electronic, and NMR spectroscopy. The data analysis indicated that the Schiff base contains bidentate nitrogen sulfur (NS) domains and was coordinated to silicon (Si) and tin (Sn) moieties via the imine-N and thiolic-S atoms, resulting in penta- and hexa-coordinated complexes in 1 : 1 and 1 : 2 ratios, respectively. The geometries around the Sn and Si atoms in complexes 1, 3, and 5 were five-coordinated and 2, 4, and 6 were six-coordinated octahedra, respectively. Density functional theory (DFT) was used to determine the optimal structural parameters. The antimicrobial activities of the ligand and its complexes were determined. These data indicate that metal complexes are more effective against bacteria and fungi in comparison to the free ligand. Molecular docking was performed to interpret the interaction of protein and various complexes and it was observed that compound 6 showed the highest binding affinity.
Assuntos
Anti-Infecciosos , Complexos de Coordenação , Compostos Orgânicos de Estanho , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Teoria da Densidade Funcional , Ligantes , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Nitrogênio , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Bases de Schiff/química , EnxofreRESUMO
In this study, chlorophenyltin(IV) [(C6H5)(Cl)Sn(L)2] and diphenyltin(IV) [(C6H5)2Sn(L)2] of N-methyl-N-hydroxyethyldithiocarbamate were prepared and characterized using various spectroscopic methods (FTIR, 1H, 13C, and 119Sn NMR) and elemental analysis. The FTIR and NMR spectral data, used to establish the structure of the compounds, showed the formation of the complexes via coordination to the two sulfur atoms from the dithiocarbamate ligand and the respective phenyltin(IV) derivatives. This coordination mode was further explored by DFT calculations, which showed that the bonding around the Sn center in [(C6H5)2Sn(L)2] was more asymmetric compared to the bonding around [(C6H5)(Cl)Sn(L)2]. However, the Sn-S bonds in [(C6H5)(Cl)Sn(L)2] were found to be more covalent than those in [(C6H5)2Sn(L)2]. Furthermore, the charge density of the frontier orbitals showed that the Sn atom in the complexes is relatively electrophilic and the Sn atom in [(C6H5)2Sn(L)2] has a lower atomic dipole moment than that of [(C6H5)(Cl)Sn(L)2]. The cytotoxicity and anti-inflammatory study revealed that [(C6H5)2Sn(L)2], with the higher number of phenyl substituents, has a higher potency than [(C6H5)(Cl)Sn(L)2]. The bio-efficacy study of these complexes as cytotoxic and anti-inflammatory agents showed that the complexes possessed moderate to high activity in comparison to the camptothecin and diclofenac in each case. Nevertheless, the diphenyltin(IV) derivative [(C6H5)2Sn(L)2] was found to possess a better activity than its counterpart due to the number of phenyl rings attached to the Sn center.
Assuntos
Compostos Orgânicos de Estanho , Cristalografia por Raios X , Teoria da Densidade Funcional , Ligantes , Espectroscopia de Ressonância Magnética , Compostos Orgânicos de Estanho/químicaRESUMO
Eight new diorganotin(IV) complexes (1a-2d), namely {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn(CH3OH)}n (1a, 2a), {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn(CH3OH)}2 (1b, 1c, 1d, 2b), and {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn}2 (2c, 2d) (X = H-, p-Me-, p-OH-, p-NO2-; R = o-Cl-C6H4CH2- or o-Me-C6H4CH2-), have been synthesized by microwave "one-pot" reaction with arylformylhydrazine, pyruvic acid, and the corresponding R2SnCl2. All the complexes have been characterized by FT-IR (Fourier transform infrared spectroscopy), multinuclear NMR (1H, 13C, and 119Sn nuclear magnetic resonance spectroscopies), HRMS (high-resolution mass spectroscopy) and single-crystal X-ray structural analysis. The antiproliferative activity of all complexes was tested against the cancer cell lines NCI-H460, MCF-7 and HepG2. The diorganotin complex 1c has been shown to be more potent antitumor agents against HepG2 than other complexes and cisplatin. Flow cytometry analysis observation demonstrated that complex 1c mediated cell apoptosis of HepG2 cells and arrested cell cycle in the S phase. The single cell gel electrophoreses assay results show that the 1c induce DNA damage. The DNA binding activities of the 1c were studied by UV-visible absorption spectrometry, fluorescence competitive, circular dichroism measurements, and molecular docking, results shown 1c can be well embedded in the groove and cleave DNA.