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1.
J Dent ; 143: 104895, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387598

RESUMO

OBJECTIVES: To compare the remineralisation efficacy and ion bioavailability of two novel SnF2-containing dentifrices in a blinded, cross-over, randomised in situ clinical study. METHODS: Six participants wore removal palatal appliances holding human enamel and dentine blocks with subsurface lesions. Appliances were worn for two treatment periods of 14 consecutive days each, with a one-week washout period in-between. Participants were randomly allocated to rinse with a 1:5 diluted coded slurry of one of two dentifrices containing either 5 % casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) +1100 ppm F as SnF2 [MIPOP], or 1100 ppm F as SnF2 [CT], for 1 min, four times a day. Saliva was collected post-treatment and analysed for tin, calcium, inorganic phosphate and fluoride ions using atomic absorption spectrophotometry and ion chromatography. Enamel and dentine lesions were analysed for percent remineralisation (%R) using transverse microradiography and percent surface microhardness recovery (%SMHR). RESULTS: MIPOP released significantly higher F (3.00 ± 0.27 mM), Ca (15.23 ± 3.23 mM) and Sn (1.18 ± 0.13 mM) into saliva whereas CT released 2.89 ± 0.32 mM F and only 0.84 ± 0.11 mM Ca and 0.28 ± 0.10 mM Sn. MIPOP produced significantly higher %R than CT: 25.6 ± 1.5 % compared to 15.2 ± 0.7 % in enamel, and 33.6 ± 3.1 % compared to 20.6 ± 1.1 % in dentine. Additionally, MIPOP produced significantly higher %SMHR (18.2 ± 7.9 %) compared to CT (4.1 ± 0.6 %). CONCLUSIONS: Both dentifrices promoted remineralisation, but the MIPOP dentifrice with added CPP-ACP and the ion-stabilising effects of CPP released higher amounts of bioavailable tin and produced significantly higher remineralisation and surface microhardness recovery. CLINICAL SIGNIFICANCE: Modern dentifrices contain SnF2 for a range of oral health benefits. Challenges associated with stability of these formulations can affect ion bioavailability, reducing efficacy. Two dentifrices with SnF2 promoted remineralisation in situ, however the dentifrice with the added saliva biomimetic CPP-ACP was superior and therefore may produce greater health benefits.


Assuntos
Dentifrícios , Fluoretos de Estanho , Humanos , Fluoretos de Estanho/farmacologia , Fluoretos de Estanho/uso terapêutico , Dentifrícios/uso terapêutico , Fluoreto de Sódio/uso terapêutico , Estanho/farmacologia , Remineralização Dentária/métodos , Fluoretos/farmacologia , Esmalte Dentário/patologia , Estudos Cross-Over , Dentina , Cariostáticos/farmacologia
2.
Caries Res ; 58(2): 81-89, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198764

RESUMO

INTRODUCTION: Erosive tooth wear is a highly prevalent dental condition that is modified by the ever-present salivary pellicle. The aim of the present in situ study was to investigate the effect of polyphenols on the ultrastructure of the pellicle formed on dentin in situ and a subsequent erosive challenge. METHODS: The pellicle was formed on bovine dentin specimens for 3 min or 2 h in 3 subjects. After subjects rinsed with sterile water (negative control), 1% tannic acid, 1% hop extract, or tin/fluoride solution containing 800 ppm tin and 500 ppm fluoride (positive control), specimens were removed from the oral cavity. The erosive challenge was performed on half of the specimens with 1% citric acid, and all specimens were analyzed by transmission electron microscopy. Incorporation of tannic acid in the pellicle was investigated by fluorescence spectroscopy. RESULTS: Compared to the negative control, ultrastructural analyses reveal a thicker and electron-denser pellicle after application of polyphenols, in which, according to spectroscopy, tannic acid is also incorporated. Application of citric acid resulted in demineralization of dentin, but to a lesser degree when the pellicle was pretreated with a tin/fluoride solution. The pellicle was more acid-resistant than the negative control when modified with polyphenols or tin/fluoride solution. CONCLUSION: Polyphenols can have a substantial impact on the ultrastructure and acid resistance of the dentin pellicle, while the tin/fluoride solution showed explicit protection against erosive demineralization.


Assuntos
Esmalte Dentário , Erosão Dentária , Humanos , Animais , Bovinos , Película Dentária , Fluoretos/farmacologia , Erosão Dentária/prevenção & controle , Estanho/farmacologia , Polifenóis/farmacologia , Fluoretos de Estanho/farmacologia , Ácido Cítrico/efeitos adversos , Dentina
3.
Drug Dev Ind Pharm ; 49(2): 168-178, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36960747

RESUMO

BACKGROUND: Hydroxyapatite (HAp) nanoparticles doped with some ions have shown anticancer and antibacterial properties and are of great interest for the development of new biomedical applications. Therefore, the present study aimed to investigate the preparation and in vitro characterization of HAp nanoparticles doped with (Ni2+), tin (Sn2+), molybdate (Mo3+) ions for prevention of infections specially in bone tissue engineering. METHODS: HAp and HAp nanocrystal powders doped with nickel (Ni2+), tin (Sn2+), molybdate ions (Mo3+) with concentrations of 500, 1000, and 2000 ppm were prepared by the sol-gel method using a combination of calcium nitrate and phosphorous pentoxide as chemical reagents. The nanoparticles were characterized by FT-IR, XRD, EDAX and SEM. Their antimicrobial effect was studied by disk diffusion method on two types of bacteria: Pseudomonas aeruginosa and Staphylococcus aureus. RESULTS: FT-IR and XRD tests confirmed the formation of HAp nanoparticles. SEM images showed the morphology and nanostructure of HAp and Ni@HAp. Ni@HAp showed significantly more antimicrobial effects than the other two ions on S. aureus. EDAX confirmed the presence of Ni2+ ions in the Ni@HAp structure and the element map also showed very good dispersion of elements in both HAp and Ni@HAp structures. CONCLUSIONS: HAp nanoparticles doped with nickel ions may be considered as a promising antibacterial treatment in bone tissue engineering and repairing of skeletal injuries contaminated with S. aureus.


Assuntos
Durapatita , Nanopartículas , Durapatita/química , Staphylococcus aureus , Níquel/farmacologia , Estanho/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Íons
4.
Front Cell Infect Microbiol ; 13: 1322778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38332949

RESUMO

The advent of nanotechnology has been instrumental in the development of new drugs with novel targets. Recently, metallic nanoparticles have emerged as potential candidates to combat the threat of drug-resistant infections. Diabetic foot ulcers (DFUs) are one of the dreadful complications of diabetes mellitus due to the colonization of numerous drug-resistant pathogenic microbes leading to biofilm formation. Biofilms are difficult to treat due to limited penetration and non-specificity of drugs. Therefore, in the current investigation, SnO2 nanoparticles were biosynthesized using Artemisia vulgaris (AvTO-NPs) as a stabilizing agent and were characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the efficacy of AvTO-NPs against biofilms and virulence factors of drug-resistant Candida albicans strains isolated from DFUs was assessed. AvTO-NPs displayed minimum inhibitory concentrations (MICs) ranging from 1 mg/mL to 2 mg/mL against four strains of C. albicans. AvTO-NPs significantly inhibited biofilm formation by 54.8%-87%, germ tube formation by 72%-90%, cell surface hydrophobicity by 68.2%-82.8%, and exopolysaccharide (EPS) production by 69%-86.3% in the test strains at respective 1/2xMIC. Biosynthesized NPs were effective in disrupting established mature biofilms of test strains significantly. Elevated levels of reactive oxygen species (ROS) generation in the AvTO-NPs-treated C. albicans could be the possible cause of cell death leading to biofilm inhibition. The useful insights of the present study could be exploited in the current line of treatment to mitigate the threat of biofilm-related persistent DFUs and expedite wound healing.


Assuntos
Artemisia , Diabetes Mellitus , Pé Diabético , Nanopartículas Metálicas , Candida albicans , Fatores de Virulência/farmacologia , Estanho/farmacologia , Azóis/farmacologia , Óxidos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química , Biofilmes , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/química
5.
Dalton Trans ; 51(34): 13119-13128, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35975724

RESUMO

Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride (Sn-DBPTF-2) anions. The complexes were characterized by standard analytical techniques and the structural details of these complexes were elucidated by single crystal X-ray diffraction. Sn-DBPTF-1 was cytotoxic at IC50 <10 µg mL-1 against cancer cell lines A549 (lung cancer), Aspc-1 (pancreatic cancer), OVCAR-3 (ovarian cancer), T-47D (breast cancer) and HCT116 (colon cancer), and breast epithelial stem cell line D492. The non-tumorigenic breast epithelial cell line MCF-10 was less sensitive at IC50 = 22 µg mL-1. Sn-DBPTF-2 had limited cytotoxic effect at IC50 13-37 µg mL-1. Sn-DBPTF-1 induced apoptosis and double-strand DNA breaks. Cell cycle arrest in G2 occurred in HCT116 and accumulation in G1 in Aspc-1. The results indicate that the basic effect of Sn-DBPTF-1 is to induce DNA damage, leading to apoptosis and cell cycle arrest depending on the cell line.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estanho/farmacologia
6.
Biomater Adv ; 137: 212819, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929256

RESUMO

Nanotechnology has immensely advanced the field of cancer diagnostics and treatment by introducing potential delivery vehicles as carriers for drugs or therapeutic agents. In due course, mesoporous silica nanoparticles (MSNs) have emerged as excellent vehicles for delivering drugs, biomolecules, and biomaterials, attributed to their solid framework and porosity providing a higher surface area for decorating with various functional ligands. Recently, the metal tin (Sn) has gained huge importance in cancer research owing to its excellent cytotoxicity and ability to kill cancer cells. In the present work, we synthesized MSNs, conjugated them with organotin compounds, and characterized them using various physicochemical techniques. Subsequently, the biological evaluation of MSN (S1), MSN-MP (S2) and tin-conjugated MSNs (S3: MSN-MP-SnPh3) (MP = 3-mercaptopropyltriethoxysilane) revealed that these nanoconjugates induced cytotoxicity, necrosis, and apoptosis in MCF-7 cells. Moreover, these nanoconjugates exhibited anti-angiogenic properties as demonstrated in the chick embryo model. The increase of reactive oxygen species (ROS) was found as a one of the plausible mechanisms underlying cancer cell cytotoxicity induced by these nanoconjugates, encouraging their application for the treatment of cancer. The tin-conjugated MSNs demonstrated less toxicity to normal cells compared to cancer cells. Furthermore, the genotoxicity studies revealed the clastogenic and aneugenic effects of these nanoconjugates in CHO cells mostly at high concentrations. These interesting observations are behind the idea of developing tin-conjugated MSNs as prospective candidates for anticancer therapy.


Assuntos
Antineoplásicos , Dióxido de Silício , Estanho , Animais , Embrião de Galinha , Cricetinae , Humanos , Antineoplásicos/farmacologia , Sobrevivência Celular , Cricetulus , Portadores de Fármacos/química , Nanoconjugados , Dióxido de Silício/química , Estanho/farmacologia
7.
Ann Plast Surg ; 89(4): 444-450, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703222

RESUMO

OBJECTIVE: Pedicled perforator partial or complete necrosis with a rate of 13.7%. This study was undertaken to test whether preconditioning with transcutaneous electrical nerve stimulation (TENS) monitored by infrared thermography protect against partial necrosis by converting the choke anastomoses to the true anastomoses via inducing heme oxygenase-1 (HO-1) in a rat pedicled perforator flap model. METHODS: Seventy-two Sprague-Dawley rats were randomly assigned to the control, the TENS, the TENS + SnPP (tin protoporphyrin; HO-1 activity inhibitor; 50 µmol/kg) and the TENS +0.9% saline groups. On the unilateral dorsum of the rats, a rectangular flap donor site of 11 × 3 cm was marked out, which contained three perforator angiosomes and two choke zones. On days 1, 3 and 4, 1 hour of TENS (biphasic pulses, 25 mA, 80 Hz, 200 µs) was applied to the flap donor sites, respectively. On day 5, after the flap donor sites were assessed by infrared thermography, the flaps were harvested based on the deep circumflex iliac artery perforator. RESULTS: Infrared thermography showed that the choke zones in the flap donor sites presented white in the TENS and the TENS +0.9% saline groups, whereas they presented red in the control and the TENS + SnPP groups. Postmortem arteriography showed that the number of arterioles across each choke zone significantly increased in the TENS and the TENS +0.9% saline groups compared with the control and the TENS + SnPP groups. Immunohistochemistry and western blot showed a significant increase in HO-1 in the choke zones after TENS preconditioning. The necrotic area percentage of the flaps was significantly decreased in the TENS (4.3% ± 2.6%) and the TENS +0.9% saline groups (4.5% ± 2.3%) compared with the control (24.8% ± 5.0%) ( P < 0.001); there was no significant difference between the TENS and the TENS + SnPP (24.4% ± 7.3%) groups. CONCLUSIONS: These data show that TENS preconditioning monitored by infrared thermography might be a promising strategy to prevent pedicled perforator flaps from partial necrosis.


Assuntos
Retalho Perfurante , Estimulação Elétrica Nervosa Transcutânea , Animais , Sobrevivência de Enxerto , Heme Oxigenase-1/farmacologia , Metaloporfirinas , Necrose , Retalho Perfurante/irrigação sanguínea , Protoporfirinas/farmacologia , Ratos , Ratos Sprague-Dawley , Solução Salina , Termografia , Estanho/farmacologia
8.
Int J Mol Sci ; 22(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34948372

RESUMO

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can be overcome by combining PDT with other methods of treatment, such as radiation therapy, neutron capture therapy, chemotherapy, etc. In this work, potential drugs were obtained for the first time, the molecules of which contain both photodynamic and chemotherapeutic pharmacophores. A derivative of natural bacteriochlorophyll a with a tin IV complex, which has chemotherapeutic activity, acts as an agent for PDT. This work presents an original method for obtaining agents of combined action, the structure of which is confirmed by various physicochemical methods of analysis. The method of molecular modeling was used to investigate the binding of the proposed drugs to DNA. In vitro biological tests were carried out on several lines of tumor cells: Hela, A549, S37, MCF7, and PC-3. It was shown that the proposed conjugates of binary action for some cell lines had a dark cytotoxicity that was significantly higher (8-10 times) than the corresponding metal complexes of amino acids, which was explained by the targeted chemotherapeutic action of the tin (IV) complex due to chlorin. The greatest increase in efficiency relative to the initial dipropoxy-BPI was found for the conjugate with lysine as a chelator of the tin cation relative to cell lines, with the following results: S-37 increased 3-fold, MCF-7 3-fold, and Hela 2.4-fold. The intracellular distribution of the obtained agents was also studied by confocal microscopy and showed a diffuse granular distribution with predominant accumulation in the near nuclear region.


Assuntos
Complexos de Coordenação/farmacologia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Estanho/farmacologia , Células A549 , Complexos de Coordenação/química , Células HeLa , Humanos , Células MCF-7 , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Porfirinas/química , Estanho/química
9.
Free Radic Res ; 55(9-10): 1018-1035, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34865583

RESUMO

Undesired toxicity and emergence of multidrug resistance (MDR) are the major impediments to the successful application of organotin-based compounds against cancer. Since oxalyl-bis(N-phenyl)hydroxamic acid (OBPHA) exerts significant efficacy against cancer, we believe that derivatives of OBPHA including organotin molecule can show a promising effect against cancer. Herein, we have selected three previously characterized OBPHA derivatives viz., succinyl-bis(N-phenyl)hydroxamic acid (SBPHA), diphenyl-tin succinyl-bis(N-phenyl)hydroxamic acid (Sn-SBPHA), malonyl-bis(N-phenyl)hydroxamic acid (MBPHA) and evaluated their antiproliferative efficacy against both drug-resistant (CEM/ADR5000; EAC/Dox) and sensitive (CCRF-CEM; HeLa; EAC/S) cancers. Data revealed that Sn-SBPHA selectively targets drug-resistant and sensitive cancers without inducing any significant toxicity to normal cells (Chang Liver). Moreover, shortening of the backbone of SBPHA enhances the efficacy of the newly formed molecule MBPHA by targeting only drug-sensitive cancers. Sn-SBPHA induces caspase3-dependent apoptosis through redox-imbalance in both drug-resistant and sensitive cancer. Sn-SBPHA also reduced the activation and expression of both MMP2 and MMP9 without altering the expression status of TIMP1 and TIMP2 in drug-resistant cancer. In addition, Sn-SBPHA reduced the activation of both STAT3 and JNK1, the transcriptional modulator of MMPs, in a redox-dependent manner in CEM/ADR5000 cells. Thus, Sn-SBPHA targets MMPs by modulating STAT3 and JNK1 in a redox-dependent manner. However, MBPHA and SBPHA fail to target drug resistance and both drug-resistant and sensitive cancer respectively. Furthermore, Sn-SBPHA significantly increases the lifespan of doxorubicin-resistant and sensitive Ehrlich Ascites Carcinoma-bearing mice without inducing any significant systemic toxicity. Therefore, Sn-SBPHA has the therapeutic potential to target and overcome MDR in cancer.


Assuntos
Ácidos Hidroxâmicos , Neoplasias , Animais , Apoptose , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Ácidos Hidroxâmicos/farmacologia , Metaloproteinases da Matriz/metabolismo , Camundongos , Neoplasias/tratamento farmacológico , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Estanho/metabolismo , Estanho/farmacologia
10.
PLoS One ; 16(7): e0254613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280212

RESUMO

The radionuclide 117mSn (tin-117m) embedded in a homogeneous colloid is a novel radiosynoviorthesis (RSO) device for intra-articular (IA) administration to treat synovial inflammation and mitigate osteoarthritis (OA) in dogs. A study to evaluate tin-117m colloid treatment response in dogs with OA was conducted at two centers, the School of Veterinary Medicine at Louisiana State University, and at a referral practice in Houston, Texas. The tin-117m colloid was administered per-protocol to 14 client-owned dogs with radiographically confirmed, grade 3 OA in one or both elbow joints. Dog owners and attending clinicians assessed the level of pain at baseline (BL) and the post-treatment pain response at 90-day intervals for one year. Owners assessed treatment response according to a pain severity score (PSS) and a pain interference score (PIS) as defined by the Canine Brief Pain Inventory. Clinicians reported a lameness score using a 0-5 scale, from no lameness to continuous non-weight bearing lameness, when observing dogs at a walk and a trot. The rate of treatment success as determined by improved mean PSS and PIS scores reported by dog owners was >70% at all time points. Clinicians reported an improved mean pain score from BL at post-treatment Days 90 (p<0.05), 180, and 270. The dog owner and clinician assessments of treatment success were significantly correlated (p>0.05) at Day 90 and Day 180 time points. Results indicated that a single IA dose of tin-117m colloid provided a significant reduction in pain and lameness and improved functionality for up to a full year, with no adverse treatment related effects, in a high percentage of dogs with advanced, clinical OA of the elbow joint.


Assuntos
Coloides/farmacologia , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Marcha/efeitos dos fármacos , Inflamação/diagnóstico por imagem , Inflamação/patologia , Inflamação/veterinária , Injeções Intra-Articulares , Isótopos/farmacologia , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Osteoartrite/veterinária , Dor/diagnóstico por imagem , Dor/patologia , Medição da Dor/métodos , Estanho/farmacologia , Resultado do Tratamento , Caminhada/fisiologia
11.
Dalton Trans ; 50(13): 4583-4592, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33705511

RESUMO

The discovery of novel anticancer chemotherapeutics is fundamental to treat cancer more efficiently. Towards this goal, two dyads consisting of a gold porphyrin appended to organotin(iv) entities were synthesized and their physicochemical and biological properties were characterized. One dyad contains a gold porphyrin connected to a tin(iv) cation via a malonate and two phenyl ligands (AuP-SnPh2), while the other contains two tin(iv) cations each chelated to one carboxylic acid group of the malonate and three phenyl ligands (AuP-Sn2Ph6). The mode of chelation of Sn(iv) to the malonate was elucidated by IR spectroscopy and 119Sn NMR. In the solid state, the complexes exist as coordination polymers in which the tin is penta-coordinated and bridged to two different malonate units. In solution the chemical shifts of 119Sn signals indicate that the tin complexes are in the form of monomeric species associated with a tetra-coordinated tin cation. The therapeutic potential of these new compounds was assessed by determining their cytotoxic activities on human breast cancer cells (MCF-7) and on healthy human fibroblasts (FS 20-68). The study reveals that the dyads are more potent anticancer drugs than the mixture of their individual components (gold porphyrin and reference tin complexes). Therefore, the covalent link of organotin complexes to a gold porphyrin induces a synergistic cytotoxic effect. The dyad AuP-SnPh2 shows high cytotoxicity (0.13 µM) against MCF-7 along with good selectivity for cancer cells versus healthy cells. Finally, it was also shown that the dyad AuP-Sn2Ph6 exhibits a very high anticancer activity (LC50 = 0.024 µM), but the presence of two tin units induces strong cytotoxicity on healthy cells too (LC50 = 0.032 µM). This study underscores, thus, the potential of the association of gold porphyrin and organotin complexes to develop anticancer metallo-drugs.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ouro/farmacologia , Malonatos/farmacologia , Porfirinas/farmacologia , Estanho/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , 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 , Ouro/química , Humanos , Malonatos/química , Estrutura Molecular , Porfirinas/química , Relação Estrutura-Atividade , Estanho/química , Células Tumorais Cultivadas
12.
Dalton Trans ; 50(6): 2177-2182, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33496304

RESUMO

A new readily-synthesized Sn(iv) tetraarylchlorin with thien-2-yl substituents (SnC) has been prepared and fully characterized by various spectroscopic techniques and its photophysical and photochemical properties, such as the singlet oxygen quantum yield (ΦΔ), fluorescence quantum yield (ΦF), triplet lifetime (τT) and photostability, have been evaluated. SnC has an unusually high ΦΔ value of 0.89 in DMF. Studies on the photodynamic activity against MCF-7 breast cancer cells exhibited a very low IC50 value of 0.9 µM and high phototoxicity (dark versus light) indices of >27.8 after irradiation with a 660 nm Thorlabs LED (280 mW cm-2). The results demonstrate that Sn(iv) tetraarylchlorins of this type are suitable candidates for further in-depth PDT studies.


Assuntos
Antineoplásicos , Neoplasias da Mama/tratamento farmacológico , Complexos de Coordenação , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Estanho , Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Feminino , Humanos , Luz , Células MCF-7 , Modelos Moleculares , Porfirinas/química , Porfirinas/farmacologia , Oxigênio Singlete/química , Estanho/química , Estanho/farmacologia
13.
Dalton Trans ; 49(28): 9568-9573, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32578634

RESUMO

Two novel Sn(iv) tetraisopropylphenylporphyrins have been synthesized to explore the effect of octabromination at the ß-pyrrole positions on their photophysical properties and photodynamic activity. The lower energy Q band of an octabrominated complex lies at 675 nm well within the therapeutic window. The octabrominated dye has a relatively high singlet oxygen quantum yield of 0.78 in DMF and exhibits favorable photodynamic activity against MCF-7 cells with an IC50 value of 10.7 µM and a 5.74 log reduction value (5 µM) towards S. aureus under illumination at 660 nm for 60 min with a Thorlabs M660L3 LED (280 mW cm-2).


Assuntos
Antineoplásicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Porfirinas/farmacologia , Estanho/química , Estanho/farmacologia
14.
Dalton Trans ; 48(16): 5183-5192, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30838370

RESUMO

Cleavage of the bromide bridges in [Pd2(µ-Br)2{κ2(Sn,As)-2-MeBrSnC6F4AsPh2}2] (1) by diphosphine ligands gave the mono- and dinuclear palladacycles [Pd(L)Br{κ2(Sn,As)-2-MeBrSnC6F4AsPh2}] [L = dppe (2) dppm (3), ortho-dppBz (4)] and [Pd2Br2(para-dppBz){κ2(Sn,As)-2-MeBrSnC6F4AsPh2}2] (5). The interactions of these complexes with DNA (CT-DNA) and proteins (human serum albumin) were studied by UV-Vis and fluorescence spectroscopy, respectively. The results confirmed the interaction of these palladium complexes with CT-DNA through groove binding, and their strong binding affinity to HSA. The anti-proliferative activities of complexes 1-5 were tested against four human cancer cell lines (HeLa, A549, PC-3, and HT1080) and normal keratinocytes (HaCaT). Among the series, the palladium(ii) complex containing the 1,2-bis(diphenylphosphino)benzene ligand (4) showed the highest cytotoxicity against HeLa, PC-3 and HT1080 cells, with IC50 values of 0.25 ± 0.08, 0.85 ± 0.11, and 0.66 ± 0.15 µM, respectively. Interestingly, compound 4 exhibited lower cytotoxic activity toward normal HaCaT cells (IC50 = 4.65 ± 0.16 µM). Additionally, this complex exhibited lower toxicity and better anti-cancer activity than cisplatin. Further mechanistic studies, including Hoechst staining and flow cytometry, confirmed that complex 4 induced G2/M phase cell cycle arrest and apoptotic cell death in HeLa cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Arsênio/química , Arsênio/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quelantes/síntese química , Quelantes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Estrutura Molecular , Paládio/química , Paládio/farmacologia , Fosfinas/química , Fosfinas/farmacologia , Relação Estrutura-Atividade , Estanho/química , Estanho/farmacologia
15.
Chem Biodivers ; 16(3): e1800633, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30629800

RESUMO

Two novel ligand-metal complexes were prepared through the reaction of Zn(II) and Sn(II) with moxifloxacin (MOX) in the presence of glycine (Gly) to investigate their biological activities. IR, UV/VIS and 1 H-NMR analysis have been carried out for insuring the chelation process. Results suggested that MOX and Gly react with the metal ions through the carbonyl oxygen atom and the oxygen atom of the carboxylic group of MOX and Gly. The antimicrobial activity was carried out against some common bacterial and fungal pathogens and the radical scavenging activity (RSA%) was evaluated using DPPH and ABTS methods. Phytotoxic effect of the prepared complexes was evaluated in vitro against Raphanus raphanistrum and Lepidium sativum. Hemolytic activity was tested against cell membrane of erythrocytes. Results showed that the two prepared complexes exhibited high antimicrobial activity against all tested phytopathogens and no significant phytotoxic effect has been observed. Only MOX-Zn(II) complex showed moderate hemolysis at 100 % concentration.


Assuntos
Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Eritrócitos/efeitos dos fármacos , Lepidium sativum/efeitos dos fármacos , Raphanus/efeitos dos fármacos , Antioxidantes/síntese química , Antioxidantes/química , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Glicina/química , Glicina/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Moxifloxacina/química , Moxifloxacina/farmacologia , Picratos/antagonistas & inibidores , Espectrofotometria Ultravioleta , Ácidos Sulfônicos/antagonistas & inibidores , Estanho/química , Estanho/farmacologia , Zinco/química , Zinco/farmacologia
16.
Mater Sci Eng C Mater Biol Appl ; 93: 996-1011, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274138

RESUMO

Herein, eco-friendly composite was synthesized by embedding silver (Ag) nanospheres onto aragonitic cuttlefish bone (CB)-stabilized samarium doped zinc oxide (Sm-doped ZnO) nanorods. The operating interaction profile and the photoactive behavior of this nanocomposite were assessed via XRD, FTIR, Raman, TEM, FE-SEM, DLS, DRS and PL techniques. Locality of Sm-doped ZnO and its attaching modes to the cuttlefish bone lamella were highly dominated by embedding Ag NPs that encouraged Zn2+ Lewis acid sites to electrostatically interact with aragonite carbonates in the channeled porous CB system. Such interacting approach enhanced photoactivity of Sm-doped ZnO by lowering its energy band gap (from 3.26 eV for Sm-doped ZnO/CB to 2.12 eV for Ag@Sm-doped ZnO/CB). Besides, plasmon-induced silver electrons provided Sm-doped ZnO by extra photosensitivity. Ag@Sm-doped ZnO/CB nanocomposite exhibited pronounced photo-activated disinfection efficiencies for Staphylococcus aureus (80%), Pseudomonas aeruginosa (60%), and Schistosoma mansoni cercariae (100%) linked with progressive demolition in cercarial body. Such nanocomposite also possessed exterminating action against Schistosoma mansoni adult worms serving near 100% worm-mortality accompanied by significant disintegration of worm body. These findings were successfully drawn Ag@Sm-doped ZnO/CB as an efficient weapon in the biocides arsenal being even capable of destructing pathogenic bacteria and parasites in dark- and photo- conditions.


Assuntos
Antibacterianos , Desinfetantes , Nanopartículas Metálicas/química , Nanocompostos/química , Nanotubos/química , Pseudomonas aeruginosa/crescimento & desenvolvimento , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomicidas , Staphylococcus aureus/crescimento & desenvolvimento , Estanho , Óxido de Zinco , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Chlorocebus aethiops , Desinfetantes/química , Desinfetantes/farmacologia , Esquistossomicidas/química , Esquistossomicidas/farmacologia , Estanho/química , Estanho/farmacologia , Células Vero , Óxido de Zinco/química , Óxido de Zinco/farmacologia
17.
Assay Drug Dev Technol ; 16(4): 205-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29878843

RESUMO

The presence of P-glycoprotein in the human intestine represents a significant barrier to effective drug therapy. These proteins form a multidrug-resistant barrier to most drugs, especially those administered orally. Thus, strategies are needed to prepare molecules to combat these resistant proteins and enable an increase in drug efficacy. We developed a novel tin-Schiff base complex using an ultrasonic bath, a new technique in small molecule synthesis. New bond formation was confirmed using ultraviolet and Fourier transform spectroscopies. A computational study was carried out using Absorption, Distribution, Metabolism, Excretion and Toxicity software. The novel tin-entecavir (ETV)-piperonal Schiff base acts as a potent P-glycoprotein inhibitor, which overcomes the multidrug resistance to all drugs that are substrates for P-glycoprotein. Further study showed that the novel tin complex is less toxic than the parent compound at the same dose. The development of this tin-piperonal-ETV Schiff base complex is a major breakthrough for overcoming multidrug resistance barriers and can be applied to other drug molecules.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Benzaldeídos/farmacologia , Benzodioxóis/farmacologia , Descoberta de Drogas , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Guanina/análogos & derivados , Estanho/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Benzaldeídos/química , Benzodioxóis/química , Guanina/química , Guanina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Bases de Schiff/química , Bases de Schiff/farmacologia , Estanho/química
18.
Eur Radiol ; 28(5): 1818-1825, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29196856

RESUMO

OBJECTIVES: To compare a low-dose, tin-filtered, nonenhanced, high-pitch Sn100 kVp CT protocol (Sn100) with a standard protocol (STP) for the detection of calcifications in the ascending aorta in patients scheduled for cardiac surgery. METHODS: Institutional Review Board approval for this retrospective study was waived and the study was HIPAA-compliant. The study included 192 patients (128 men; age 68.8 ± 9.9 years), of whom 87 received the STP and 105 the Sn100 protocol. Size-specific dose estimates (SSDE) and radiation doses were obtained using dose monitoring software. Two blinded readers evaluated image quality on a scale from 1 (low) to 5 (high) and the extent of calcifications of the ascending aorta on a scale from 0 (none) to 10 (high), subdivided into 12 anatomic segments. RESULTS: The Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy and 0.20 ± 0.04 mSv compared with the mean SSDE of 5.4 ± 2.2 mGy achieved with the STP protocol (p < 0.0001). Calcification burden was associated with age (p < 0.0001), but was independent of protocol with mean calcification scores of 0.48 ± 1.23 (STP) and 0.55 ± 1.25 (Sn100, p = 0.18). Reader agreement was very good (STP κ = 0.87 ± 0.02, Sn100 κ = 0.88 ± 0.01). The STP protocol provided a higher subjective image quality than the Sn100 protocol: STP median 4, interquartile range 4-5, vs. SN100 3, 3-4; p < 0.0001) and a slightly better depiction of calcification (STP 5, 4-5, vs. Sn100 4, 4-5; p < 0.0001). CONCLUSIONS: The optimized Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy while the depiction of calcifications remained good, and there was no systematic difference in calcification burden between the two protocols. KEY POINTS: • Tin-filtered, low-dose CT can be used to assess aortic calcifications before cardiac surgery • An optimized Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy • The depiction of atherosclerosis of the thoracic aorta was similar with both protocols • The depiction of relevant thoracic pathologies before cardiac surgery was similar with both protocols.


Assuntos
Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Radiografia Torácica/métodos , Estanho/farmacologia , Calcificação Vascular/diagnóstico , Idoso , Aorta Torácica/efeitos da radiação , Feminino , Humanos , Masculino , Doses de Radiação , Estudos Retrospectivos
19.
Bull Environ Contam Toxicol ; 98(5): 607-611, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27904927

RESUMO

This study evaluated the effect of tin exposure on enzyme activity in the sea cucumber (Holothuria grisea Selenka, 1867). After exposure to 0 (control), 0.04, 0.08, or 0.12 mg L-1 tin, we tested the activities of total cholinesterase in longitudinal muscles, acid phosphatase in gonads and the respiratory tree, as well as alkaline phosphatase in the intestines during a 96-h bioassay. Regression analyses showed that all enzyme activities declined with increasing tin concentrations, except for acid phosphatase in the respiratory tree, which were similarly, inhibited at all tin concentrations. These results indicate that H. grisea is a potential bioindicator for seascape habitat monitoring programs, as its biochemical markers show sensitivity to trace elements that can indicate a rise in pollution levels.


Assuntos
Fosfatase Ácida/antagonistas & inibidores , Fosfatase Alcalina/antagonistas & inibidores , Inibidores da Colinesterase/farmacologia , Holothuria/enzimologia , Estanho/farmacologia , Animais , Relação Dose-Resposta a Droga , Gônadas/enzimologia , Intestinos/enzimologia , Músculos/enzimologia , Sistema Respiratório/enzimologia
20.
Dalton Trans ; 45(44): 17929-17938, 2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27779268

RESUMO

The Schiff base H2L1 [N,N'-ethylenebis(3-methoxysalicylaldimine)] or H2L2 [N,N'-ethylenebis(3-ethoxysalicylaldimine)] was reacted with MCl2·xH2O and SnCl4·5H2O to afford the supramolecular heterobimetallic systems (H2ED)2+·2[ML]·[SnCl6]2- [M = Cu, L = L1 (1), L = L2 (2); M = Ni, L = L1 (3), L = L2 (4); ED = 1,2-ethylenediamine], whose structures were established by single crystal X-ray analyses. Each structure includes different entities, viz. a mononuclear [CuL]/[NiL] neutral complex (coformer), a hexachlorostannate dianion [SnCl6]2-, a 1,2-ethylenediammonium dication (H2ED2+) and, only in 2 and 4, a methanol molecule. Based on the work of Grothe et al. (Cryst. Growth Des., 2016, 16, 3237-3243), compounds 1 and 3 are cocrystal salts, 2 and 4 are cocrystal salt solvates. The ionic pairs (H2ED)2+·[SnCl6]2- in 1-4 are encapsulated by the Cu- or Ni-complexes, and stabilized by N-HO and one N-HCl bond interactions leading to infinite 1D chains. The antimicrobial studies of 1-4 against yeasts (C. albicans and S. cerevisiae) and Gram-positive (S. aureus and E. faecalis) and -negative bacteria (P. aeruginosa and E. coli) indicate that the Ni2Sn systems (3 and 4) are more active than the analogous Cu2Sn ones (1 and 2).


Assuntos
Anti-Infecciosos/química , Complexos de Coordenação/química , Cobre/química , Níquel/química , Bases de Schiff/química , Estanho/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Candidíase/tratamento farmacológico , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Cristalização , Cristalografia por Raios X , Humanos , Modelos Moleculares , Níquel/farmacologia , Bases de Schiff/farmacologia , Estanho/farmacologia , Leveduras/efeitos dos fármacos
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