Antiviral activity against Zika virus of a new formulation of curcumin in poly lactic-co-glycolic acid nanoparticles.

OBJECTIVES: In the search of an effective antiviral formulation, the natural product curcumin (CUR) was encapsulated into poly(lactic-co-glycolic acid) nanoparticles, a non-toxic bioresorbable and biocompatible copolymer. The resulting CUR containing particles (PLGA-CUR NPs) were characterized and analysed for antiviral activity against Zika virus (ZIKV) infection. METHODS: The PLGA-CUR NPs were characterized by Fourier transform infrared, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy and thermogravimetric analysis and release profile. Cytotoxicity of PLGA-CUR and the antiviral activity against ZIKV were determined in Vero cells. The effect of PLGA-CUR NPs on viral RNA synthesis and protein expression was analysed by RT-qPCR and immunofluorescence staining, respectively. KEY FINDINGS: The PLGA-CUR NPs showed an appropriate in vitro drug release profile. Our studies of the antiviral activity of PLGA-CUR NPs and CUR against ZIKV by virus yield reduction as well as viral RNA synthesis and protein expression have shown that PLGA-CUR formulation is more effective than free CUR to inhibit ZIKV infection of Vero cells. CONCLUSIONS: Our results demonstrate for the first time the antiviral activity against ZIKV of PLGA nanoparticles charged with CUR, suggesting that PLGA-CUR NPs are promising candidates for a drug formulation against human pathogenic flaviviruses.

Development of carbohydrate functionalized magnetic nanoparticles for aminoglycosides magnetic solid phase extraction.

Magnetic nanoparticles decorated with d-galactose and galactitol (Fe3O4@SiN-galactose and Fe3O4@SiN-galactitol) were synthesized and employed as sorbent in a magnetic solid phase extraction (MSPE) procedure prior the analysis of aminoglycosides (AGs) in honey samples by LC-MS/MS. AGs are broad spectrum antibiotics, characterized by aminosugars, widespread used in therapeutic and veterinary applications. AGs can be found in the environment and food of animal origin. Fe3O4@SiN-galactose and Fe3O4@SiN-galactitol were synthesized via copper catalyzed alkyne azide cycloaddition and the synthesis was efficiently followed by infrared spectroscopy. They were characterized by electron microscopy, thermogravimetric analysis and magnetization curves. The nature of the loading (acetonitrile:water, 50:50 v/v) and elution solution (formic acid 190 mM) were studied in order to optimize the MSPE. Quantitative difference between MSPE with Fe3O4@SiN-galactose and MSPE with Fe3O4@SiN-galactitol in terms of recovery was found. The final optimized method using Fe3O4@SiN-galactose and Fe3O4@SiN-galactitol was applied in the determination of AGs in honey. The MSPE performance of Fe3O4@SiN-galactitol was found to be superior to that of MSPE with Fe3O4@SiN-galactose. The limits of quantification were between 2 and 19 µg kg-1 for amikacin, dihydrostreptomycin, tobramicyn and gentamycin. A good correlation between predicted and nominal values of AGs in honey was found (trueness from 84% to 109%). This MSPE procedure not only requires a minimum amount of sorbent (1 mg) and sample (0.2 g), but it can also be accomplish in a rather short time.

Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological properties.

Fused heterobicyclic systems have gained much importance in the field of medicinal chemistry because of their broad spectrum of physiological activities. Among the heterocyclic rings containing bridgehead nitrogen atom, imidazothiazoles derivatives are especially attractive because of their different biological activities. Since many imidazothiazoles derivatives are effective for treating several diseases, is interesting to analyze the behavior of some isosteric related heterocycles, such as pirrolothiazoles, imidazothiadiazoles and imidazotriazoles. In this context, this review summarizes the current knowledge about the syntheses and biological behavior of these families of heterocycles. Traditional synthetic methodologies as well as alternative synthetic procedures are described. Among these last methodologies, the use of multicomponent reaction, novel and efficient coupling reagents, and environmental friendly strategies, like microwave assistance and solvent-free condition in ionic liquids are also summarized. This review includes the biological assessments, docking research and studies of mechanism of action performed in order to obtain the compounds leading to the development of new drugs.

Synthesis of imidazo[2,1-b]thiazoles linked to an unprotected carbohydrate moiety.

Two series of imidazo[2,1-b]thiazoles substituted on C-3 or C-5 with an unprotected carbohydrate moiety were synthesized. Different protective groups for position 3 of the carbohydrate moiety were tested (acetyl, tert-butyldimethylsilyl (TBDMS), and p-methoxybenzyl (PMB)) and the latter turn out to be the best strategy to obtain the desired products. Full deprotection of the carbohydrate was performed successfully in only one step.