RESUMEN
Quinoline core has been shown to possess a promising role in the development of anticancer agents. However, the correlation between its broad spectrum of bioactivity and the underlying mechanism of actions is poorly understood. The present study, with the use of bioinformatics approaches, reported a series of designed molecules which integrated quinoline core and sulfonyl moiety, with the objective of evaluating the substituent and linker effects on anticancer activities and associated mechanistic targets. We identified potent compounds (1h, 2h, 5 and 8) exhibiting significant anticancer effects towards liver cancer cells (Hep3B) with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) relative values of cytotoxicity below 0.40, a value in the range of doxorubicin positive control with the value of 0.12. Bulky substituents and the presence of bromine atom, as well as the presence of sulfonamide linkage, are likely the favorable structural components for molecules exerting a strong anticancer effect. To the best of our knowledge, our findings obtained from chemical synthesis, in vitro cytotoxicity, bioinformatics-based molecular docking analysis (similarity ensemble approach, SEA),and electrophoretic mobility shift assay provided the first evidence in correlation to the anticancer activities of the selected compound 5 with the modulation on the binding of transcription factor NF-κB to its target DNA. Accordingly, compound 5 represented a lead structure for the development of quinoline-based NF-κB inhibitors and this work added novel information on the understanding of the mechanism of action for bioactive sulfonyl-containing quinoline compounds against hepatocellular carcinoma.
RESUMEN
Nanotechnology manipulates therapeutic agents at the nanoscale for the development of nanomedicines. However, there are current concerns over nanomedicines, mainly related to the possible toxicity of nanomaterials used for health medications. Due to their small size, they can enter the human body more readily than larger sized particles. Green chemistry encompasses the green synthesis of drug-loaded nanoparticles by reducing the use of hazardous materials in the synthesis process, thus reducing the adverse health impacts of pharmaceutics. This would greatly expand their potential in biomedical treatments. This review highlights the potential risks of nanomedicine formulations to health, delivery routes of green nanomedicines, recent advances in the development of green nanoscale systems for biomedical applications and future perspectives for the green development of nanomedicines.
Asunto(s)
Portadores de Fármacos/efectos adversos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Tecnología Química Verde/métodos , Nanopartículas/efectos adversos , Nanopartículas/química , Nanotecnología/métodos , Animales , Portadores de Fármacos/toxicidad , Humanos , Nanomedicina/métodos , Nanopartículas/toxicidadRESUMEN
In this study, a novel green microencapsulation system was used to develop Phyllanthus urinaria (PU) extract containing microcapsules. Agar was used with gelatin as the wall matrix materials of microcapsules to prevent the use of toxic crosslinker formaldehyde. Microencapsulated PU extract was developed to improve the potential antifungal activities of PU water extracts. The active components and surface morphology of PU extract containing microcapsules were analyzed by liquid chromatography/mass spectrometry and scanning electron microscopy, respectively. The in vitro release study demonstrated that approximately 80% of drug was released after 120 h. PU loaded microcapsules were shown to have a stronger anti-Aspergillus niger activity than the free drug.
Asunto(s)
Aspergillus niger , Composición de Medicamentos , Phyllanthus/química , Extractos Vegetales , Agar/química , Antifúngicos/química , Antifúngicos/farmacología , Aspergillus niger/efectos de los fármacos , Aspergillus niger/patogenicidad , Cápsulas/química , Cápsulas/farmacología , Gelatina/química , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications.
Asunto(s)
Cápsulas/química , Sistemas de Liberación de Medicamentos/métodos , Administración Oral , Administración Tópica , Animales , Quitosano , Fluorouracilo , Hidrocortisona , Queratinocitos/citología , Ratones , Piel/citología , Piel/efectos de los fármacos , Staphylococcus aureus , Ácido SuccínicoRESUMEN
Chitosan based microcapsule which encapsulated with phyllanthin was developed by simple coacervation. The composition and surface morphology of phyllanthin containing microcapsules were analyzed by Fourier Transform Infrared spectroscopy and Scanning Electron Microscopy, respectively. The release of phyllanthin from the microcapsules was found to be more than 60% after 120 h. In vitro biological assays demonstrated that these phyllanthin containing microcapsules showed a stronger anti-oxidation potential on both human fibroblasts and keratinocytes as well as a better growth inhibitory activity towards Staphylococcus aureus.
Asunto(s)
Cápsulas/química , Fibroblastos/metabolismo , Queratinocitos/metabolismo , Lignanos/química , Microscopía Electrónica de Rastreo/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/metabolismo , Antibacterianos/farmacología , Antioxidantes/química , Química Farmacéutica/métodos , Quitosano/química , Diseño de Fármacos , Humanos , Modelos Químicos , Especies Reactivas de Oxígeno , Propiedades de Superficie , Factores de TiempoRESUMEN
The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules administration lead to a significant inhibition of cyclooxygenase-2 protein expression in the hepatocytes when compared with vehicle control mice. Interestingly, microcapsule containing celecoxib showed a better inhibition of cyclooxygenase-2 protein expression when compared with a simple oral administration of free celecoxib. Gas-chromatography-mass-spectrometry analysis showed that in mice treated with free celecoxib or chitosan/celecoxib microcapsules, their plasma concentration of celecoxib was similar. Microcapsules-based biomaterials as oral drug delivery vehicles may help to improve the absorption efficiency of therapeutic drugs.