RESUMO
In the present study, the effect of sulfonamide-chalcone 185 (SSC185) was investigated against B16-F10 metastatic melanoma cells aggressive actions, besides migration and adhesion processes, by in silico and in vitro assays. In silico studies were used to characterize the pharmacokinetic profile and possible targets of SSC185, using the pkCSM web server, and docking simulations with AutoDock Tools. Furthermore, the antimetastatic effect of SSC185 was investigated by in vitro experiments using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony, scratch, and cell adhesion assays, and atomic force microscopy (AFM). The molecular docking results show better affinity of SSC185 with the metalloproteinases-2 (MMP-2) and α5ß1 integrin. SSC185 effectively restricts the formation of colonies, migration, and adhesion of B16-F10 metastatic melanoma cells. Through the AFM images changes in cells morphology was identified, with a decrease in the filopodia and increase in the average cellular roughness. The results obtained demonstrate the potential of this molecule in inhibit the primordial steps for metastasis, which is responsible for a worse prognosis of late stage cancer, being the main cause of morbidity among cancer patients.
Assuntos
Adesão Celular , Movimento Celular , Chalcona , Simulação de Acoplamento Molecular , Sulfonamidas , Movimento Celular/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Sulfonamidas/farmacologia , Sulfonamidas/química , Camundongos , Animais , Linhagem Celular Tumoral , Chalcona/farmacologia , Chalcona/química , Chalcona/análogos & derivados , Metaloproteinase 2 da Matriz/metabolismo , Melanoma Experimental/patologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Microscopia de Força Atômica , Antineoplásicos/farmacologia , Antineoplásicos/química , Chalconas/farmacologia , Chalconas/química , HumanosRESUMO
Epiisopiloturine (EPI) is a compound found in jaborandi leaves with antiparasitic activity, which can be enhanced when incorporated into nanoparticles (NP). Cashew Gum (CG), modified by carboxymethylation, is used to produce polymeric nanomaterials with biological activity. In this study, we investigated the antimicrobial potential of carboxymethylated CG (CCG) NP containing EPI (NPCCGE) and without the alkaloid (NPCCG) against bacteria and parasites of the genus Leishmania. We conducted theoretical studies, carboxymethylated CG, synthesized NP by nanoprecipitation, characterized them, and tested them in vitro. Theoretical studies confirmed the stability of modified carbohydrates and showed that the EPI-4A30 complex had the best interaction energy (-8.47 kcal/mol). CCG was confirmed by FT-IR and presented DSabs of 0.23. NPCCG and NPCCGE had average sizes of 221.94 ± 144.086 nm and 247.36 ± 3.827 nm, respectively, with homogeneous distribution and uniform surfaces. No NP showed antibacterial activity or cytotoxicity to macrophages. NPCCGE demonstrated antileishmanial activity against L. amazonensis, both in promastigote forms (IC50 = 9.52 µg/mL, SI = 42.01) and axenic amastigote forms (EC50 = 6.6 µg/mL, SI = 60.60). The results suggest that nanostructuring EPI in CCG enhances its antileishmanial activity.
Assuntos
Anacardium , Anti-Infecciosos , Nanopartículas , Gomas Vegetais , Anacardium/química , Nanopartículas/química , Gomas Vegetais/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Animais , Camundongos , Leishmania/efeitos dos fármacos , Simulação por Computador , Imidazóis , 4-Butirolactona/análogos & derivadosRESUMO
In this study, two nanoemulsions were formulated with essential oil (EO) of Ocimum gratissimum with (EON) or without (EOE) cashew gum (CG). Subsequently, inhibition of melanosis and preservation of the quality of shrimp stored for 16 days at 4 ± 0.5 °C were evaluated. A computational approach was performed to predict the system interactions. Dynamic light scattering (DLS) and atomic force microscopy (AFM) were used for nanoparticle analysis. Gas chromatography and flame ionization detector (GC-FID) determined the chemical composition of the EO constituents. Shrimps were evaluated according to melanosis's appearance, psychrotrophic bacteria's count, pH, total volatile basic nitrogen, and thiobarbituric acid reactive substances. EON exhibited a particle size three times smaller than EOE. The shrimp treated with EON showed a more pronounced sensory inhibition of melanosis, which was considered mild by the 16th day. Meanwhile, in the other groups, melanosis was moderate (EOE) or severe (untreated group). Both EON and EOE treatments exhibited inhibition of psychrotrophic bacteria and demonstrated the potential to prevent lipid oxidation, thus extending the shelf life compared to untreated fresh shrimp. EON with cashew gum, seems more promising due to its physicochemical characteristics and superior sensory performance in inhibiting melanosis during shrimp preservation.
Assuntos
Anacardium , Ocimum , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Ocimum/química , Anacardium/química , Penaeidae/química , Gomas Vegetais/química , Conservação de Alimentos/métodosRESUMO
OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.
Assuntos
Mucosa Esofágica , Refluxo Gastroesofágico , Humanos , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/prevenção & controle , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Mucosa Esofágica/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Permeabilidade , Impedância Elétrica , Administração Tópica , Biopolímeros , Idoso , Fluoresceína/administração & dosagem , Esôfago/efeitos dos fármacos , Esôfago/patologia , Esôfago/metabolismo , Azia/tratamento farmacológico , Azia/prevenção & controle , Relevância ClínicaRESUMO
Docetaxel (DTX) is a non-selective antineoplastic agent with low solubility and a series of side effects. The technology of pH-sensitive and anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes aims to increase the selective delivery of the drug in the acidic tumor environment to cells with EFGR overexpression. Thus, the study aimed to develop pH-sensitive liposomes based on DOPE (dioleoylphosphatidylethanolamine) and CHEMS (cholesteryl hemisuccinate), using a Box-Behnken factorial design. Furthermore, we aimed to conjugate the monoclonal antibody cetuximab onto liposomal surface, as well as to thoroughly characterize the nanosystems and evaluate them on prostate cancer cells. The liposomes prepared by hydration of the lipid film and optimized by the Box-Behnken factorial design showed a particle size of 107.2 ± 2.9 nm, a PDI of 0.213 ± 0.005, zeta potential of -21.9 ± 1.8 mV and an encapsulation efficiency of 88.65 ± 20.3%. Together, FTIR, DSC and DRX characterization demonstrated that the drug was properly encapsulated, with reduced drug crystallinity. Drug release was higher in acidic pH. The liposome conjugation with the anti-EGFR antibody cetuximab preserved the physicochemical characteristics and was successful. The liposome containing DTX reached an IC50 at a concentration of 65.74 nM in the PC3 cell line and 28.28 nM in the DU145 cell line. Immunoliposome, in turn, for PC3 cells reached an IC50 of 152.1 nM, and for the DU145 cell line, 12.60 nM, a considerable enhancement of cytotoxicity for the EGFR-positive cell line. Finally, the immunoliposome internalization was faster and greater than that of liposome in the DU145 cell line, with a higher EGFR overexpression. Thus, based on these results, it was possible to obtain a formulation with adequate characteristics of nanometric size, a high encapsulation of DTX and liposomes and particularly immunoliposomes containing DTX, which caused, as expected, a reduction in the viability of prostate cells, with high cellular internalization in EGFR overexpressing cells.
RESUMO
Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 105 g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications.
Assuntos
Adenocarcinoma , Citrus , Masculino , Animais , Camundongos , Humanos , Próstata , Galactanos , Adenocarcinoma/tratamento farmacológicoRESUMO
Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.
Assuntos
Anacardium , Nanopartículas , Trypanosoma cruzi , Reprodutibilidade dos Testes , Nanopartículas/química , Liberação Controlada de Fármacos , Polímeros/farmacologia , Concentração de Íons de Hidrogênio , Portadores de Fármacos/farmacologiaRESUMO
We developed a new hydrophobic polymer based on angico gum (AG), and we produced new nanoparticles to expand the applications of natural polysaccharides in nanomedicine. Phthalate angico gum (PAG) was characterized by 1H NMR, FTIR, elementary analysis, solubility, XRD, and TG. PAG was a hydrophobic and semi-crystalline material, a relevant characteristic for drug delivery system applications. As a proof of concept, nevirapine (NVP) was selected for nanoparticles development. Plackett-Burman's experimental design was used to understand the influence of several factors in nanoparticles production. PAG proved to be a versatile material for producing nanoparticles with different characteristics. Optimized nanoparticles were produced using desirability parameters. NVP-loaded PAG nanoparticles formulation showed 202.1 nm of particle size, 0.23 of PDI, -17.1 of zeta potential, 69.8 of encapsulation efficiency, and promoted modified drug release for 8 h. Here we show that PAG presents as a promising biopolymer for drug delivery systems.
Assuntos
Química Verde , Nanopartículas/química , Nanotecnologia , Ácidos Ftálicos/química , Gomas Vegetais/química , Liberação Controlada de Fármacos , Humanos , Microscopia de Força Atômica , Peso Molecular , Nevirapina/farmacologia , Tamanho da Partícula , Espectroscopia de Prótons por Ressonância Magnética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios XRESUMO
Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.
Assuntos
Anacardium/química , Sistemas de Liberação de Medicamentos , Gomas Vegetais/química , Doença de Chagas/tratamento farmacológico , Simulação por Computador , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Micro-Ondas , Estrutura Molecular , Nanopartículas/química , Nitroimidazóis/administração & dosagem , Tamanho da Partícula , Ácidos Ftálicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tripanossomicidas/administração & dosagemRESUMO
Aminated poly(N-isopropylacrylamide) (PNIPAm-NH2) was grafted onto oxidized galactomannan polysaccharide extracted from Delonix regia (OXGM) via Schiff base reaction by a simple, rapid synthetic route, deprived of the use of organic solvents. Grafting was confirmed by FTIR and 1H NMR and the self-organizing ability of the obtained nanoparticle copolymers was investigated by dynamic light scattering (DLS). The minimum concentration required for self-organization (CAC) at 25 °C was higher than at 50 °C. Lower critical solution temperature (LCST) was in the range 34-40 °C, depending on both inserted PNIPAm-NH2 molar mass and on the presence of reduced imine bond. Synthesized copolymers are promising candidates for drug delivery as they show good cell viability, particle size around 250 nm and transition temperature closer to that of human body. Reaction success points out to the possibility of use free aldehyde groups of oxidized polysaccharide, not used in the copolymerization, to form a pro-drug with substances that possess NH2 groups in their structure, such as doxorubicin.
Assuntos
Resinas Acrílicas/química , Materiais Biocompatíveis/síntese química , Fabaceae/química , Mananas/química , Galactose/análogos & derivados , Polimerização , Bases de Schiff/química , Sementes/química , Temperatura de TransiçãoRESUMO
Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone obtained from Auxemma oncocalyx (Allem) Taub has several biological effects; however, there is no data on its antimicrobial action. In this study, its antimicrobial and antibiofilm activities were evaluated against bacteria and fungi of clinical interest. Strains of Gram-positive and Gram-negative bacteria, and filamentous fungi and yeasts were selected to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of oncocalyxone A. The antibacterial effect of oncocalyxone A was studied using survival curves, atomic force microscopy (AFM), and the involvement of oxidative stress. We examined the inhibitory action of the molecule on biofilm formation and its hemolytic activity against human erythrocytes. Our results showed that among the strains tested, Staphylococcus epidermidis was highly sensitive to the action of oncocalyxone A, with an MIC of 9.43 µg/mL. In most bacterial strains analyzed, a bacteriostatic effect was observed, though the molecule showed no antifungal activity. Antibiofilm activity was observed against the methicillin-resistant S. aureus bacteria. Additionally, results from atomic force microscopy imaging showed that oncocalyxone A significantly altered bacterial morphology. Further, oncocalyxone A showed no hemolytic activity at concentrations ≥151 µg/mL. Together, our results demonstrate the antibacterial and antibiofilm potential of oncocalyxone A, indicating its therapeutic potential against bacterial resistance.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antraquinonas , Antibacterianos/farmacologia , Benzoquinonas/farmacologia , Biofilmes , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade MicrobianaRESUMO
In the present work, we investigated the minimal inhibitory concentration (MIC) against fungal strains (Fonsecaea pedrosoi, Microsporum canis, Candida albicans, Cryptococcus neoformans), and cytotoxicity to normal cell lines for modified red angico gum (AG) with eterifying agent N-chloride (3-chloro-2-hydroxypropyl) trimethylammonium (CHPTAC). Quaternized ammonium groups were linked to AG backbone using N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride. The chemical features of the quaternized gum derivatives (QAG) were analyzed by: FTIR, elemental analysis, Zeta potential and gel permeation chromatography. The angico quaternizated gum presented a degree of substitution (DS) of 0.22 and Zeta potential of +36.43. For the antifungal test, it was observed that unmodified gum did not inhibit fungal growth. While, QAG inhibited the growth of most fungi used in this study. By AFM technique QAG interacted with the fungal surface, altering wall roughness significantly. The probable affinity of fragments of the QAG structure for the fungal enzyme 5I33 (Adenylosuccinate synthetase) has been shown by molecular docking. Low cytotoxicity was observed for polymers (unmodified gum and QAG). The results demonstrate that the quaternized polymer of AG presented in this study is a quite promising biomaterial for biotechnological applications.
Assuntos
Antifúngicos , Citotoxinas , Inibidores Enzimáticos , Fabaceae/química , Proteínas Fúngicas , Fungos/enzimologia , Simulação de Acoplamento Molecular , Polissacarídeos , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Células HEK293 , Humanos , Ligases/antagonistas & inibidores , Ligases/química , Camundongos , Polissacarídeos/química , Polissacarídeos/farmacologiaRESUMO
Introduction: Photodynamic therapy (PDT) is a process that uses a light source (e.g. laser), oxygen molecules and a photosensitizing agent. PDT aims to act against pathogens, including those resistant to antimicrobials. The association of PDT with natural drugs, such as Propolis, has not been widely studied. Methods: Therefore, this study aimed to evaluate the antimicrobial effect of PDT in vitro by using Propolis as a photosensitizing agent. For this purpose, the dry Propolis extract was used as a photosensitizer and a low-power laser (Photon Laser III model) was irradiated onto the microwells for 90 seconds. Gram-positive and Gram-negative bacterial strains were used in the tests at a concentration of 5 × 105 CFU/mL. Initially, the antibacterial activity of the photosensitizers without laser action was determined by using a serial microdilution method before the experiment with a laser. After the incubation of the plates in a bacteriological oven, resazurin (0.1%) was added and the minimum inhibitory concentration (MIC) was determined. Alterations in the morphology of the bacteria were analysed by using atomic force microscopy (AFM). Results: Bacteria were sensitive to Propolis with MICs ranging from 13.75 to 0.85 mg/mL, but no susceptibility was observed for methylene blue without laser application. A change was observed for MIC values of Propolis against Staphylococcus aureus after irradiation, which decreased from 1.71 mg/mL to 0.85 mg/mL. However, this behaviour was not observed in Escherichia coli, the only gram-negative strain used. In addition, AFM images revealed alterations in the size of one of the bacteria tested. Conclusion: The Propolis is more active against gram-positive bacteria and PDT improved its activity against one of the strains tested.