Supramolecular hydrogels of β-cyclodextrin linked to calcium homopoly-L-guluronate for release of coumarins with trypanocidal activity

© 2018 Elsevier Ltd Association constants and thermodynamicsparameters on inclusion of four 3-amido coumarins that present trypanocidal activity, into 6-amino-β-cyclodextrin (1:1 stoichimetry) were determined. In addition, pure homopolymeric-α-L-guluronate fraction prepared by partial hydrolysis of sodium alginate from Sub-Antarctic Kelp Durvillaea antarctica was conjugated with 6-amino-β-cyclodextrin (64% yield). To glycoconjugates, 3-amido coumarins were incorporated (73% of encapsulation) and supramolecular hydrogels were prepared by gelation with Ca2+ ions. The trypanocidal activity of the inclusion complexes increased by 10%. Likewise, an increase in diffusion in artificial membrane was observed (13%). It was found that the inclusion complexes increased the variation of the mitochondrial potential of T. cruzi (17%). The lowest release of substituted amidocoumarins (ACS) from supramolecular hydrogels occurred at pH 1.2 whereas the maximum release (34%) was observed at pH 8.0. Enca

Chemical structure and biological properties of sulfated fucan from the sequential extraction of subAntarctic Lessonia sp (Phaeophyceae)

This work is related to the structural characterization of the sulfated polysaccharide from Lessonia sp and the study of its antioxidant and antiparasitic properties. Sequential extraction afforded D-mannitol as the only low MW sugar alcohol. Extraction with 2% CaCl2 afforded in 3.0% yield, a sulfated fucan (SF). Its major fraction (48.5% yield), isolated by ion-exchange chromatography corresponds to a linear polymer of α-l-fucopyranosil residues linked 1→3, sulfated at the O-4 and partially at O-2 positions. By alkaline extraction, sodium alginate (10.3% yield) was obtained. The antioxidant capacity of SF by ESR showed high elimination index (IC50, mg/mL) of hydroxyl (0.27), alkoxy (10.05), and peroxyl (82.88) radicals in relation to commercial mannitol. SF showed activity against the epimastigote form of Trypanosoma cruzi parasite (250 μg/mL) and low cytotoxicity in murine cells (367 μg/mL). The elimination capacity of radicals in aqueous medium of SF would allow its potential biomedical application.status: publishe

Evaluation of trypanocidal and antioxidant activities of a selected series of 3-amidocoumarins

Background: Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease. Objectives: With the aim of finding new trypanocidal agents, we report the in vitro evaluation of a new series of 3-amidocoumarins with or without hydroxyl substituents at position 4 of the coumarin ring. Methods: Electrochemical and biological assays were performed in order to assess the antioxidant and trypanocidal potential of these compounds and to better understand the mechanisms involved in their activity. Results: Most of the studied compounds showed high trypanocidal activity against both epimastigote and trypomastigote forms, with IC50 values in the low micromolar range. Some of them have greater activity and selectivity than the reference compound, nifurtimox. Conclusion: Compound 2 is the most active of this series, being also non-cytotoxic against murine RAW 264.7 macrophages. Electrochemical and radical scavenging experiments were carried out, providing new information about the profile of the best derivatives, and the potential therapeutic application of the new 3-amidocoumarin

Chemical structure and biological properties of sulfated fucan from the sequential extraction of subAntarctic Lessonia sp (Phaeophyceae)

© 2018 Elsevier Ltd This work is related to the structural characterization of the sulfated polysaccharide from Lessonia sp and the study of its antioxidant and antiparasitic properties. Sequential extraction afforded D-mannitol as the only low MW sugar alcohol. Extraction with 2% CaCl2 afforded in 3.0% yield, a sulfated fucan (SF). Its major fraction (48.5% yield), isolated by ion-exchange chromatography corresponds to a linear polymer of α-L-fucopyranosil residues linked 1→3, sulfated at the O–4 and partially at O–2 positions. By alkaline extraction, sodium alginate (10.3% yield) was obtained. The antioxidant capacity of SF by ESR showed high elimination index (IC50, mg/mL) of hydroxyl (0.27), alkoxy (10.05), and peroxyl (82.88) radicals in relation to commercial mannitol. SF showed activity against the epimastigote form of Trypanosoma cruzi parasite (250 μg/mL) and low cytotoxicity in murine cells (367 μg/mL). The elimination capacity of radicals in aqueous medium of SF would allo

Evaluation of trypanocidal properties of ferrocenyl and cyrhetrenyl N-acylhydrazones with pendant 5-nitrofuryl group.

Four N-acylhydrazones of general formulae [R1-C(O)-NH-N=C(R2)(5-nitrofuryl)] with (R1 = ferrocenyl or cyrhetrenyl and R2 = H or Me) are synthesized and characterized in solution and in the solid-state. Comparative studies of their stability in solution under different experimental conditions and their electrochemical properties are reported. NMR studies reveal that the four compounds are stable in DMSO‑d6 and complementary UV-Vis studies confirm that they also exhibit high stability in mixtures DMSO:H2O at 37 °C. Electrochemical studies show that the half-wave potential of the nitro group of the N-acylhydrazones is smaller than that of the standard drug nifurtimox and the reduction process follows a self-protonation mechanism. In vitro studies on the antiparasitic activities of the four complexes and the nifurtimox against Trypanosoma cruzi and Trypanosoma brucei reveal that: i) the N-acylhydrazones have a potent inhibitory growth activity against both parasites [EC50 in the low micromolar (in T. cruzi) or even in the nanomolar (in T. brucei) range] and ii) cyrhetrenyl derivatives are more effective than their ferrocenyl analogs. Parallel studies on the L6 rat skeletal myoblast cell line have also been conducted, and the selectivity indexes determined. Three of the four N-acylhydrazones showed higher selectivity towards T. brucei than the standard drug nifurtimox. Additional studies suggest that the organometallic compounds are bioactivated by type I nitroreductase enzymes

Comparison of chemical and biological properties of organometallic complexes containing 4- and 5-nitrothienyl groups

This study compares the nitro group position of thienyl imines bound to organometallic fragments, and the respective electrochemical and anti-parasitic properties. Ferrocenyl and cyrhetrenyl imines derived from 4-nitrothiophene (1a-3a) and 5-nitrothiophene (1b-3b) were synthesized and characterized by spectroscopic techniques. In addition, molecular structure of 1a, 2a and 3a were determined by X-ray crystallography

Determination of Antioxidant Activity by Oxygen Radical Absorbance Capacity (ORAC-FL), Cellular Antioxidant Activity (CAA), Electrochemical and Microbiological Analyses of Silver Nanoparticles Using the Aqueous Leaf Extract of Solanum mammosum L.

[Purpose] The importance of studying polyphenolic compounds as natural antioxidants has encouraged the search for new methods of analysis that are quick and simple. The synthesis of silver nanoparticles (AgNPs) using plant extracts has been presented as an alternative to determine the total polyphenolic content and its antioxidant activity.[Methods] In this study, aqueous leaf extract of Solanum mammosum, a species of plant endemic to South America, was used to produce AgNPs. The technique of oxygen radical absorption capacity using fluorescein (ORAC-FL) was used to measure antioxidant activity. The oxidation of the 2´,7´-dichlorodihydrofluorescein diacetate (DCFH2-DA) as fluorescent probe was used to measure cellular antioxidant activity (CAA). Electrochemical behavior was also examined using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Total polyphenolic content (TPH) was analyzed using the Folin-Ciocalteu method, and the major polyphenolic compound was analyzed by high performance liquid chromatography with diode array detector (HPLC/DAD). Finally, a microbial analysis was conducted using Escherichia coli and Bacillus sp.[Results] The average size of nanoparticles was 5.2 ± 2.3 nm measured by high-resolution transmission electron microscopy (HR-TEM). The antioxidant activity measured by ORAC-FL in the extract and nanoparticles were 3944 ± 112 and 637.5 ± 14.8 μM ET/g of sample, respectively. Cellular antioxidant activity was 14.7 ± 0.2 for the aqueous extract and 12.5 ± 0.2 for the nanoparticles. The electrochemical index (EI) was 402 μA/V for the extract and 324 μA/V for the nanoparticles. Total polyphenolic content was 826.6 ± 20.9 and 139.7 ± 20.9 mg EGA/100 g of sample. Gallic acid was the main polyphenolic compound present in the leaf extract. Microbiological analysis revealed that although leaf extract was not toxic for Escherichia coli and Bacillus sp., minor toxic activity for AgNPs was detected for both strains.[Conclusion] It is concluded that the aqueous extract of the leaves of S. mammosum contains nontoxic antioxidant compounds capable of producing AgNPs. The methods using AgNPs can be used as a fast analytical tool to monitor the presence of water-soluble polyphenolic compounds from plant origin. Analysis and detection of new antioxidants from plant extracts may be potentially applicable in biomedicine.This research was funded by the Pontificia Universidad Católica del Ecuador www.puce.edu.ec