RESUMEN
Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/ß-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/ß-CD, and hydrogen bonds along with π-π stacking interactions are responsible for the better stability, especially for (MMC)2@ß-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@ß-CD (FL) and (MMC)2@ß-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@ß-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.
Asunto(s)
Cumarinas , Cicatrización de Heridas , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Cumarinas/química , Cumarinas/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Humanos , Solubilidad , MasculinoRESUMEN
Palm seedlings are visually selected from mature fruits in a slow process that leads to nonuniform germination and high embryo mortality. In this study, we determined the levels of monosaccharides, their crystallinity, and their role in the formation of Euterpe edulis endosperm during seed maturation. Seeds harvested from 108 to 262 days after anthesis (DAA) were analyzed morphologically, physiologically, and chemically to measure soluble and insoluble lignins, ashes, structural carbohydrates, degree of crystallinity, and endo-ß-mannanase. The seeds achieved maximum germination and vigor at 164 DAA. During the early stages, only compounds with a low structural order were formed. The contents of soluble and insoluble lignins, ashes, glucans, and galactans decreased during maturation. Those of mannans, the main structural carbohydrate in the endosperm, increased along with the degree of crystallinity, as suggested by a mannan-I-type X-ray diffraction pattern. Similarly, endo-ß-mannanase activity peaked at 262 DAA. The superior physiological outcome of seeds and seedlings at 164 DAA implies a 98-day shorter harvesting time. The state of mannans during seed maturation could be used as a marker to improve seedling production by E. edulis.
Asunto(s)
Arecaceae , Germinación , Mananos , Semillas , Semillas/crecimiento & desarrollo , Semillas/química , Mananos/química , Arecaceae/química , Arecaceae/crecimiento & desarrollo , Árboles , Lignina/química , Lignina/metabolismo , Endospermo/química , Endospermo/metabolismo , Plantones/crecimiento & desarrolloRESUMEN
The discovery of new drugs and dosage forms for the treatment of neglected tropical diseases, such as human and animal leishmaniasis, is gaining interest in the chemical, biological, pharmaceutical, and medical fields. Many pharmaceutical companies are exploring the use of old drugs to establishing new drug dosage forms and drug delivery systems, in particular for use in neglected diseases. The formation of complexes with cyclodextrins is widely used to improve the stability, solubility, and bioavailability of pharmaceutical drugs, as well as reduce both the toxicity and side effects of many of these drugs. The aim of this study was to characterize solid compounds obtained from the association between furazolidone (FZD) and ß-cyclodextrin (ß-CD) or hydroxypropyl-ß-cyclodextrin (HP-ß-CD). The solid compounds were prepared in molar ratios of 1:1 and 1:2 (drug:CD) by kneading and lyophilization. Molecular docking was used to predict the preferred relative orientation of FZD when bound in both studied cyclodextrins. The resulting solid compounds were qualitatively characterized by scanning electron microscopy (SEM), thermal analysis (DSC and TG/DTG), X-ray diffraction (XRD), Raman spectroscopy with image mapping (Raman mapping), and 13C nuclear magnetic resonance spectroscopy (13C NMR) in the solid state. The cytotoxicity of the compounds against THP-1 macrophages and the 50% growth inhibition (IC50) against Leishmania amazonensis promastigote forms were subsequently investigated using in vitro techniques. For all of the solid compounds obtained, the existence of an association between FZD and CD were confirmed by one or more characterization techniques (TG/DTG, DSC, SEM, XRD, RAMAN, and 13C NMR), particularly by a significant decrease in the crystallinity of these materials and a reduction in the melting enthalpy associated with furazolidone thermal events. The formation of more effective interactions occurred in the compounds prepared by lyophilization, in a 1:2 molar ratio of the two CDs studied. However, the formation of an inclusion complex was confirmed only for the solid compound obtained from HP-ß-CD prepared by lyophilization (LHFZD1:2). The absence of cytotoxicity on the THP-1 macrophage lineages and the leishmanicidal activity were confirmed for all compounds. MHFZD1:2 and LHFZD1:2 were found to be very active against promastigote forms of L. amazonensis, while all others were considered only active. These results are in line with the literature, demonstrating the existence of biological activity for associations between drugs and CDs in the form of complexes and non-complexes. All solid compounds obtained were found to be promising for use as leishmanicidal agents against promastigote forms of L. amazonensis.
Asunto(s)
Antiprotozoarios/farmacología , Furazolidona , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Rastreo Diferencial de Calorimetría , Leishmania/efectos de los fármacos , Simulación del Acoplamiento Molecular , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
The current study aimed obtaining antimicrobial sachets that could be used as preservatives for foods. Basil (BEO) and Pimenta dioica (PDEO) essential oils (EOs) were analyzed by GC-FID and GC-MS and tested against the foodborne bacteria S. aureus, E. coli, L. monocytogenes, P. aeruginosa, S. Enteritidis, and the food-spoilage mold B. nivea. Then, inclusion complexes (ICs) with EOs and ß-cyclodextrin (ß-CD) were prepared as a strategy to reduce volatility and increase the release time of EOs. Eight ICs were prepared by kneading and freeze-drying methods, in two molar ratios, and have been characterized by complementary methods: FT-IR, thermal analysis (DSC and TG/DTG), powder XRD, and solid state 13C NMR. In vitro antimicrobial activities of ICs, both dispersed in agar and loaded in sachets, have also been investigated. Complexation was confirmed for all samples. PDEO-based ICs prepared by kneading method, at both molar ratios, displayed better in vitro antimicrobial activity. The obtained results strongly suggest a potential application of these ICs as natural antimicrobials.
Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Conservantes de Alimentos/química , Conservantes de Alimentos/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología , Brasil , Escherichia coli/efectos de los fármacos , Conservación de Alimentos/métodos , Liofilización , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Ocimum basilicum/química , Pimenta/química , Staphylococcus aureus/efectos de los fármacos , Difracción de Rayos XRESUMEN
Este estudo teve como objetivo avaliar o tipo e a localização dos defeitos nas superfícies dos instrumentos rotatórios antes e depois de seu uso no preparo de canais radiculares, in vitro. Quarenta molares inferiores e superiores humanos foram preparados com oito jogos de instrumentos rotatórios ProTaper® Universal (Dentsply Maillefer, Switzerland), rotação constante de 350 rpm. Os instrumentos foram avaliados de D0 a D3 ao microscópio eletrônico de varredura (Superscan SS-550, Shimadzu, Japão) em três momentos: Grupo A û antes do uso dos instrumentos; Grupo B û após o uso de cada série de instrumentos no preparo de três dentes; Grupo C û pelas mesmas séries de alargadores no preparo de mais dois molares. As alterações de superfície foram classificadas como marcas de frenagem, tiras de metal, arestas cortantes rombas e depressões. Os alargadores analisados descritivamente antes da instrumentação mostraram marcas de frenagem e tiras de metal no primeiro e terceiro milímetros. Depressões foram predominantes no segundo milímetro. No segundo momento, marcas de frenagem; tiras de metal e depressões foram predominantes no primeiro milímetro. E no terceiro momento, depressões estiveram presentes em todos os milímetros de cada instrumento estudado. Os alargadores que sofreram deformidades significativas foram Sx, S1 e F1 no milímetro D0-D1; F3 e F4 no milímetro D1-D2; e F5 no milímetro D2-D3. O tempo não influenciou nos resultados encontrados. Conclui-se que os defeitos nos instrumentos estavam presentes na superfície dos alargadores ao longo dos 3 mm estudados. Com a instrumentação, a quantidade de alargadores que apresentou arestas cortantes rombas e depressões progrediu.