RESUMEN
Microbial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; ~25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 µM against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 µM. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.
Asunto(s)
Alternaria/metabolismo , Antineoplásicos Fitogénicos/farmacología , Cardenólidos/aislamiento & purificación , Biotransformación , Cardenólidos/farmacocinética , Cardenólidos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Humanos , Análisis Espectral/métodosRESUMEN
Active food packaging has become attractive because of the possibility to provide a longer shelf-life by loading functional agents into the packages to maintain the quality of food products. Herein, photoluminescent and transparent polyvinyl alcohol (PVA)-based composites embedding multicolor fluorescent carbon dots (CD/PVA) were prepared by the solvent casting method. The prepared CDs emit a strong and stable fluorescence in solution while the CD/PVA composite films were transparent, flexible, and showed UV-blocking activity with a strong fluorescence emission. Blue color-emitting CDs showed the highest UV blockage at UVA (87.04%), UVB (87.04%), and UVC (92.22%) regions while PVA alone absorbed only less than 25% of the light in all UV regions. UV blockage capacity was shown to be decreased by half, in line with the emission color shift from blue to red. Thermal properties of the PVA film were improved by the addition of CDs to the polymer, and in vitro cell viability tests showed that none of the CDs were cytotoxic against the human lung fibroblast healthy cell line (MRC-F cells) when integrated into the PVA. The antimicrobial activity of CD/PVA nanofilms was qualitatively determined. The prepared films exhibited good antimicrobial activity against both Gram-positive and Gram-negative bacteria with mild antioxidant and metal chelating activity, and significant inhibition of biofilm formation with a strong link with emitted color and the concentration of the composites. Green- and red-emitting CD/PVA with the highest antimicrobial activity were then analyzed and compared with the plane PVA employing their effect on the shelf-life of strawberries as a model for perishable foods. Fresh strawberries dip coated with CD/PVA and PVA were monitored over time, and virtual evaluations showed that CDs/PVA film coating resulted in reduced weight and moisture loss and significantly inhibited the fungal growth and spoiling for over 6 days at RT and 12 days at fridge conditions maintaining the visual appearance and natural color of the fruit. The findings in this work indicated the potential of reported CD as non-cytotoxic, UV-blocking antimicrobial additives for the development of edible coatings and packages for their use in the food industry, as well as pharmaceutical and healthcare applications.
RESUMEN
Polyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Streptomyces , Antibacterianos/farmacología , Ionóforos , Pruebas de Sensibilidad MicrobianaRESUMEN
In this manuscript, the researches on the Event-Related Potentials (ERP) elicited by the standard Stroop effect were reviewed. For the sake of clarity, only the parts of the manuscripts that reported the standard Stroop effect - ERPs relation were taken into consideration.
RESUMEN
This study aimed at producing silk fibroin (SF)/hyaluronic acid (HA) and olive leaf extract (OLE) nanofibers with sheath/core morphology by coaxial electrospinning method, determining their antimicrobial properties, and examining release profiles of OLE from these coaxial nanofibers. Optimum electrospinning process and solution parameters were determined to obtain uniform and bead-free coaxial nanofibers. Scanning electron microscopy and transmission electron microscopy (TEM) were used to characterize the morphology of the nanofibers. The antimicrobial activities of nanofibers were tested according to AATCC test method 100. Total phenolic content and total antioxidant activity were tested using in vitro batch release system. The quality and quantity of released components of OLE were determined by high-performance liquid chromatography. The changes in nanofibers were examined by Fourier-transform infrared spectroscopy. Uniform and bead-free nanofibers were produced successfully. TEM images confirmed the coaxial structure. OLE-loaded nanofibers demonstrated almost perfect antibacterial activities against both of gram-negative and gram-positive bacteria. Antifungal activity against C. albicans was rather poor. After a release period of 1 month, it was observed that â¼70-95% of the OLE was released from nanofibers and it was still bioactive. Overall results indicate that the resultant shell/core nanofibers have a great potential to be used as biomaterials.