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Hypothesis: The possibility to use hexamethylenediamine (HMDA) to impart film forming ability to natural polymers including eumelanins and plant polyphenols endowed with biological activity and functional properties has been recently explored with the aim to broaden the potential of polydopamine (PDA)-based films overcoming their inherent limitations. 5,6-dihydroxyindole-2-carboxylic acid, its methyl ester (MeDHICA) and eumelanins thereof were shown to exhibit potent reducing activity. Experiments: MeDHICA and HMDA were reacted in aqueous buffer, pH 9.0 in the presence of different substrates to assess the film forming ability. The effect of different reaction parameters (pH, diamine chain length) on film formation was investigated. Voltammetric and AFM /SEM methods were applied for analysis of the film redox activity and morphology. HPLC, MALDI-MS and 1HNMR were used for chemical characterization. The film reducing activity was evaluated in comparison with PDA by chemical assays and using UV stressed human immortalized keratinocytes (HaCat) cells model. Findings: Regular and homogeneous yellowish films were obtained with moderately hydrophobic properties. Film deposition was optimal at pH 9, and specifically induced by HMDA. The film consisted of HMDA and monomeric MeDHICA accompanied by dimers/small oligomers, but no detectable MeDHICA/HMDA covalent conjugation products. Spontaneous assembly of self-organized networks held together mainly by electrostatic interactions of MeDHICA in the anion form and HMDA as the dication is proposed as film deposition mechanism. The film displayed potent reducing properties and exerted significant protective effects from oxidative stress on HaCaT

New neutral carbene complexes of gold(I) [Au(Im-Me)X] (X = Cl, Au1; X = Br, Au2; X = I, Au3) have been synthesized and fully characterized by different techniques, including NMR and UV-vis absorption spectroscopy and single crystal X-ray diffraction. The carbene ligand Im-Me is decorated with a glucoside fragment via a triazole linker, obtainable through a click chemistry reaction. The compounds retain the Au-NHC fragment in aqueous solvents, and an equilibrium between the neutral halo- and the cationic di-carbene form [Au(Im-Me)2]+ is observed, whose extent follows the trend Au1 < Au2 < Au3. Cytotoxicity studies on two cancer and two non-tumorigenic cell lines reflect the solution behavior, as a certain difference among the complexes was disclosed, with the iodo complex Au3 being more active and selective. The compounds interact with both DNA and protein model systems. The X-ray structure of the adduct formed upon the reaction of Au1 with bovine pancreatic ribonuclease (RNase A) reveals Au binding at the side chain of His105 of both protein molecules A and B of the asymmetric unit. The binding of gold atoms at both the nitrogen atoms of the imidazole ring of His15 and at the N-terminal tail has been found in the adduct formed with hen egg white lysozyme.

This study describes new platinum(II) cationic five-coordinate complexes (1-R,R’) of the formula [PtR(NHC)(dmphen)(ethene)]CF3SO3 (dmphen = 2,9-dimethyl-1,10-phenanthroline), containing in their axial positions an alkyl group R (methyl or octyl) and an imidazole-based NHC-carbene ligand with a substituent R’ of variable length (methyl or octyl) on one nitrogen atom. The Pt–carbene bond is stable both in DMSO and in aqueous solvents. In DMSO, a gradual substitution of dmphen and ethene is observed, with the formation of a square planar solvated species. Octanol/water partitioning studies have revealed the order of hydrophobicity of the complexes (1-Oct,Me > 1-Oct,Oct > 1-Me,Oct > 1-Me,Me). Their biological activity was investigated against two pairs of cancer and non-cancer cell lines. The tested drugs were internalized in cancer cells and able to activate the apoptotic pathway. The reactivity of 1-Me,Me with DNA and protein model systems was also studied using UV–vis absorption spectroscopy, fluorescence, and X-ray crystallography. The compound binds DNA and interacts in various ways with the model protein lysozyme. Remarkably, structural data revealed that the complex can bind lysozyme via non-covalent interactions, retaining its five-coordinate geometry.

Hydrophobic molecules, in particular, carotenoids, have been directly extracted from Synechococcus bigranulatus ACUF680 by means of secondary amine switchable solvent N-ethylbutylamine (EBA) without any other pretreatment. EBA was able to extract hydrophobic molecules from both fresh and frozen biomass at the same extent of the conventional procedure (about 20% of dry biomass). In particular, selective extraction of a zeaxanthin-enriched fraction (green fraction, GF) and a β-carotene-enriched fraction (orange fraction, OF) was obtained. The ratio between zeaxanthin and β-carotene was 4.4 ± 1.5 for GF, 0.07 ± 0.06 for OF, and about 1 for conventional extraction. These fractions showed in vitro antioxidant activity (IC50 values of 0.056 ± 0.013 and 0.024 ± 0.008 mg mL-1 for GF and OF, respectively) and biocompatibility on immortalized cells. Moreover, OF and GF were able to protect cells from oxidative stress, both before and after thermal treatment. Results clearly indicate that EBA is a good candidate to specifically extract β-carotene and zeaxanthin from the wet biomass of S. bigranulatus without affecting their biological activity. Skipping energy-intensive operations to break the cells and using either fresh or frozen biomass may be the driving factors to use EBA switchable solvent on an industrial scale.

Here, an unprecedented biorefinery approach has been designed to recover high-added value bioproducts starting from the culture of Porphyridium cruentum. This unicellular marine red alga can secrete and accumulate high-value compounds that can find applications in a wide variety of industrial fields. 300 ± 67 mg/L of exopolysaccharides were obtained from cell culture medium; phycoerythrin was efficiently extracted (40% of total extract) and isolated by a single chromatography, with a purity grade that allowed the crystal structure determination at 1.85 Å; a 2-fold increase in β-carotene yield was obtained from the residual biomass; the final residual biomass was found to be enriched in saturated fatty acids. Thus, for the first time, a complete exploitation of P. cruentum culture was set-up.

We have previously demonstrated that the Thymus algeriensis and Thymus fontanesii extracts have powerful anti-inflammatory, antipyretic, and analgesic effects against acute pain models. We profiled their chemical composition and found many phenolic acids, flavonoids, and phenolic diterpenes. In this work, we investigated their antioxidant properties on HaCaT cells exposed to UVA-induced oxidative stress and examined their effects against chronic neuropathic pain and the underlying mechanisms. Through a rat chronic constriction injury (CCI) model, we induced chronic neuropathic pain by placing 4 loose ligatures around the right sciatic nerve for 14 days. Thermal and mechanical hyperalgesia in addition to cold and dynamic allodynia were tested on the day before surgery and on the 7th and 14th post-surgery days. Key markers of the nitrosative and oxidative stresses, in addition to markers of inflammation, were measured at day 14 post surgery. Histopathological examination and immunostaining of both synaptophysin and caspase-3 of sciatic nerve and brain stem were also performed. Results of this study showed that T. algeriensis extract suppresses UVA oxidative stress in HaCaT cells via activation of the Nrf-2 pathway. Both extracts attenuated hyperalgesia and allodynia at 7- and 14-days post-surgery with more prominent effects at day 14 of surgery. Their protective effects against neuropathic pain were mediated by inhibiting NOX-1, iNOS, by increasing the enzyme activity of catalase, and inhibition of inflammatory mediators, NF-κB, TNF-α, lipoxygenase, COX-2 enzymes, and PGE2. Furthermore, they improved deleterious structural changes of the brainstem and sciatic nerve. They also attenuated the increased caspase-3 and synaptophysin. The data indicate that both extracts have neuroprotective effects against chronic constriction injury-induced neuropathic pain. The observed protective effects are partially mediated through attenuation of oxidative and nitrosative stress and suppression of both neuroinflammation and neuronal apoptosis, suggesting substantial activities of both extracts in amelioration of painful peripheral neuropathy.

Auoxo3 is a gold(iii) compound endowed with cytotoxic activity towards a variety of malignant cells. Encapsulation of Auoxo3 within horse spleen ferritin (Ft) improves the selectivity of the gold compound towards cancer cells over normal cells. In the current work, the changes in protein expression are presented in response to MCF-7 stimulation with Auoxo3-encapsulated Ft versus the free Au(iii) compound by a label-free proteomics approach. A 159-protein dataset showed significant changes between the stimulations with Auoxo3 and Auoxo3-encapsulated Ft, suggesting that this cellular perturbation caused the alteration of different cellular processes. In detail, roughly 30% of proteins were downregulated mainly in the spliceosome complex (U2AF1, SF3B2, PRPF4, SNSRP200, EFTUD2, PRPF6, and PRPF8) in agreement with the cytostatic effect observed during cellular growth. Another 30% of proteins were upregulated primarily in glutathione biosynthesis, suggesting an alteration of the redox potential, as validated by Western blot analyses. To the best of our knowledge, this work represents the first large scale proteomics study on the effects of a gold-based drug encapsulated within the Ft nanocage on cancer cells.

Microalgae started receiving attention as producers of third generation of biofuel, but they are rich in many bioactive compounds. Indeed, they produce many molecules endowed with benefic effects on human health which are highly requested in the market. Thus, it would be important to fractionate algal biomass into its several high-value compounds: this represents the basis of the microalgal biorefinery approach. Usually, conventional extraction methods have been used to extract a single class of molecules, with many side effects on the environment and on human health. The development of a green downstream platform could help in obtaining different class of molecules with high purity along with low environmental impact. This review is focused on technical advances that have been performed, from classic methods to the newest and green ones. Indeed, it is fundamental to set up new procedures that do not affect the biological activity of the extracted molecules. A comparative analysis has been performed among the conventional methods and the new extraction techniques, i.e., switchable solvents and microwave-assisted and compressed fluid extractions.

Amyloidoses are characterized by the accumulation and aggregation of misfolded proteins into fibrils in different organs, leading to cell death and consequent organ dysfunction. The specific substitution of Leu 75 for Pro in Apolipoprotein A-I protein sequence (ApoA-I; L75P-ApoA-I) results in late onset amyloidosis, where deposition of extracellular protein aggregates damages the normal functions of the liver. In this work, we describe that the autophagic process is inhibited in the presence of the L75P-ApoA-I amyloidogenic variant in stably transfected human hepatocyte carcinoma cells. The L75P-ApoA-I amyloidogenic variant alters the redox status of the cells, resulting into excessive mitochondrial stress and consequent cell death. Moreover, L75P-ApoA-I induces an impairment of the autophagic flux. Pharmacological induction of autophagy or transfection-enforced overexpression of the pro-autophagic transcription factor EB (TFEB) restores proficient proteostasis and reduces oxidative stress in these experimental settings, suggesting that pharmacological stimulation of autophagy could be a promising target to alleviate ApoA-I amyloidosis.

Apolipoprotein A-I (ApoA-I) amyloidosis is a rare protein misfolding disease where fibrils of the N-terminal domain of the protein accumulate in several organs, leading to their failure. Although ApoA-I amyloidosis is systemic, the different amyloidogenic variants show a preferential tissue accumulation that appears to correlate with the location of the mutation in the protein sequence and with the local extracellular microenvironment. However, the factors leading to cell/tissues damage, as well as the mechanisms behind the observed organ specificity are mostly unknown. Therefore, we investigated the impact of ApoA-I variants on cell physiology and the mechanisms driving the observed tissue specificity. We focused on four ApoA-I amyloidogenic variants and analyzed their cytotoxicity as well as their ability to alter redox homeostasis in cell lines from different tissues (liver, kidney, heart, skin). Moreover, variant-specific interactions with extracellular matrix (ECM) components were measured by synchrotron radiation circular dichroism and enzyme-linked immunosorbent assay. Data indicated that ApoA-I variants exerted a cytotoxic effect in a time and cell-type-specific manner that seems to be due to protein accumulation in lysosomes. Interestingly, the ApoA-I variants exhibited specific preferential binding to the ECM components, reflecting their tissue accumulation pattern in vivo. While the binding did not to appear to affect protein conformations in solution, extended incubation of the amyloidogenic variants in the presence of different ECM components resulted in different aggregation propensity and aggregation patterns.

The demand for natural antioxidants to be used in food industry is increasing, as synthetic antioxidants are toxic and have high production costs. Specifically, food processing and preservation require antioxidants resistant to thermal sterilization processes. In this study, twenty-five strains among microalgae and cyanobacteria were screened as antioxidants producers. The species Enallax sp., Synechococcus bigranulatus and Galdieria sulphuraria showed the highest content of chlorophyll a and total carotenoids. In vitro stability and antioxidant activity of the ethanolic extracts were performed. The results revealed that pigments present in the extracts, obtained from the previously mentioned species, were stable at room temperature and exhibited in vitro free radical scavenging potential with IC50 values of 0.099 ± 0.001, 0.048 ± 0.001 and 0.13 ± 0.02 mg mL-1, respectively. Biocompatibility assay showed that the extracts were not toxic on immortalized cell lines. The antioxidant activity was also tested on a cell-based model by measuring intracellular ROS levels after sodium arsenite treatment. Noteworthy, extracts were able to exert the same protective effect, before and after the pasteurization process. Results clearly indicate the feasibility of obtaining biologically active and thermostable antioxidants from microalgae. Green solvents can be used to obtain thermo-resistant antioxidants from cyanobacteria and microalgae which can be used in the food industry. Thus, the substitution of synthetic pigments with natural ones is now practicable. Graphical abstract: [Figure not available: see fulltext.].

Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficacy. The drug-loaded ferritins were characterized via UV-vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy to assess AF encapsulation and to define the exact amount of gold atoms trapped in the Ft cavity. The crystal structures allowed us to define the nature of AF interaction with both ferritins and to identify the gold binding sites. Moreover, the biological characterization let us to obtain preliminary information on the cytotoxic effect of AF when bound to the human H-chain.

This article describes the synthesis, characterization, and biological activity of novel square-planar cationic platinum(II) complexes containing glucoconjugated triazole ligands and a comparison with the results obtained from the corresponding five-coordinate complexes bearing the same triazole ligands. Stability in solution, reactivity with DNA and small molecules of the new compounds were evaluated by NMR, fluorescence, and UV–vis absorption spectroscopy, together with their cytotoxic action against pairs of immortalized and tumorigenic cell lines. The results show that the square-planar species exhibit greater stability than the corresponding five-coordinate ones. Furthermore, although the square-planar complexes are less cytotoxic than the latter ones, they exhibit a certain selectivity. These results simultaneously demonstrate that overall stability is a fundamental prerequisite for preserving the performance of the agents and that coordinative saturation constitutes a point in favor of their biological action.

This study was designed to evaluate the optimal conditions for the eco-friendly synthesis of silver nanoparticles (AgNPs) using

The effects of encapsulating the cytotoxic dinuclear trithiolato-bridged arene ruthenium complex [(η6 -p-MeC6 H4 iPr)2 Ru2 (μ2 -S-p-C6 H4 tBu)3 ]Cl (DiRu-1) within the apoferritin (AFt) nanocage were investigated. The DiRu-1-AFt nanocarrier was characterized by UV/Vis spectroscopy, ICP-MS, CD and X-ray crystallography. In contrast to previously reported Au- and Pt-based drug-loaded AFt carriers, we found no evidence of direct interactions between DiRu-1 and AFt. DiRu-1-AFt is cytotoxic toward immortalized murine BALB/c-3T3 fibroblasts transformed with SV40 virus (SVT2) and human epidermoid carcinoma A431 malignant cells, and exhibits moderate selectivity for these cancer cells over normal BALB/c-3T3 cells. DiRu-1-AFt triggers the production of reactive oxygen species, depolarization of mitochondrial membrane potential, and induces cell death via p53-mediated apoptosis. Comparison between our data and previous results suggests that the presence of specific interactions between a metal-based drug and AFt within the protein cage is not essential for drug encapsulation.

The setup of an economic and sustainable method to increase the production and commercialization of products from microalgae, beyond niche markets, is a challenge. Here, a cascade approach has been designed to optimize the recovery of high valuable bioproducts starting from the wet biomass of Galdieria phlegrea. This unicellular thermo-acidophilic red alga can accumulate high-value compounds and can live under conditions considered hostile to most other species. Extractions were performed in two sequential steps: a conventional high-pressure procedure to recover phycocyanins and a solvent extraction to obtain fatty acids. Phycocyanins were purified to the highest purification grade reported so far and were active as antioxidants on a cell-based model. Fatty acids isolated from the residual biomass contained high amount of PUFAs, more than those recovered from the raw biomass. Thus, a simple, economic, and high effective procedure was set up to isolate phycocyanin at high purity levels and PUFAs.

Pompe disease is a metabolic myopathy due to acid alpha‐glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha‐glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model and in patients’ cells. In cells, stress levels inversely correlated with the ability of rhGAA to correct the enzymatic deficiency. Antioxidants (N‐acetylcysteine, idebenone, resveratrol, edaravone) improved alpha‐glucosidase activity in rhGAA‐treated cells, enhanced enzyme processing, and improved mannose‐6‐phosphate receptor localization. When co‐administered with rhGAA, antioxidants improved alpha‐glucosidase activity in tissues from the Pompe disease mouse model. These results indicate that oxidative stress impacts on the efficacy of enzyme replacement therapy in Pompe disease and that manipulation of secondary abnormalities may represent a strategy to improve the efficacy of therapies for this disorder., Enzyme replacement therapy (ERT) with recombinant human alpha‐glucosidase (rhGAA) is currently the standard of care for the treatment of Pompe disease. However, this approach shows important limitations. We have tested whether modulation of oxidative stress may improve the efficacy of ERT.

This study was designed to evaluate the optimal conditions for the eco-friendly synthesis of silver nanoparticles (AgNPs) using Lythrum salicaria L. (Lythraceae) aqueous extracts and their potential application and safe use. AgNPs synthesized using L. salicaria aerial parts (LSA-AgNPs) and root extract (LSR-AgNPs) were characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM/EDS), and X-ray powder diffraction (XRPD). Dynamic light scattering (DLS) was used for the determination of the size distribution profiles of the obtained nanoparticles. Both L. salicaria extracts showed high phenolic content, while the flavone C-glucosides orientin, vitexin, and isovitexin were detected in extracts using HPLC. The synthesized AgNPs displayed growth inhibition of the tested bacteria and fungi in concentrations between 0.156 and 1.25 mg mL−1. The studied nanoparticles also showed antioxidant potential and gained selectivity at different concentrations on different cancer cell lines. Concentrations of LSA-AgNPs were found to be 20.5 and 12 μg mL−1 towards A431 and SVT2, respectively, while LSR-AgNPs were effective only against A431 cancer cells (62 μg mL−1). The hemolytic activity of LSA-AgNPs in concentrations up to 150 μg mL−1 was not observed, while LSR-AgNPs in the highest applied concentration hemolyzed 2.8% of erythrocytes. The degradation possibility of Congo red and 4-nitrophenol using LSA-AgNPs and LSR-AgNPs as catalysts was also proven. The results indicate that L. salicaria may be used for the eco-friendly synthesis of AgNPs with possible applications as antimicrobial and selective cytotoxic agents towards cancer cell lines, as well as in catalytic degradation of pollutants.

Several plant extracts are acquiring increasing value because of their antioxidant activity and hypolipidemic properties. Among them, great interest has been recently paid to a&ccedil, ai fruit as a functional food. The aim of this study was to test the ability of a&ccedil, ai extract in reducing oxidative stress and modulating lipid metabolism in vitro using different cell models and different types of stress. In fact, lipid peroxidation as evaluated in a HepG2 model was reduced five-fold when using 0.25 &micro, g/mL of extract, and it was further reduced (20-fold) with the concentration increase up to 2.5 &micro, g/mL. With the non alcoholic fatty liver disease (NAFLD)in vitro model, all concentrations tested showed at least a two-fold reduced fat deposit. In addition, primary adipocytes challenged with TNF-&alpha, under hypoxic conditions to mimic the persistent subcutaneous fat, treated with a&ccedil, ai extract showed an approximately 40% reduction of fat deposit. Overall, our results show that a&ccedil, ai is able to counteract oxidative states in all the cell models analysed and to prevent the accumulation of lipid droplets. No toxic effects and high stability overtime were highlighted at the concentrations tested. Therefore, a&ccedil, ai can be considered a suitable support in the prevention of different alterations of lipid and oxidative metabolism responsible for fat deposition and metabolic pathological conditions.

Bioapplications of 2D materials embrace demanding features in terms of environmental impact, toxicity and biocompatibility. Here we report on the use of a rationally modified lysozyme to assist the exfoliation of MoS2 bulk crystals suspended in water through ultrasonic exfoliation. The design of the proposed lysozyme derivative provides this exfoliated 2D-materail with both, hydrophobic groups that interact with the surface of MoS2 and hydrophilic groups exposed to the aqueous medium, which hinders its re-aggregation. This approach, clarified also by molecular docking studies, leads to a stable material (ζ-potential, 27 ± 1 mV) with a yield of up to 430 µg ml−1. The bio-hybrid material was characterized in terms of number of layers and optical properties according to different slots separated by diverse centrifugal forces. Furthermore the obtained material was proved to be biocompatible using human normal keratinocytes and human cancer epithelial cells, whereas the method was demonstrated to be applicable to produce other 2D materials such as graphene. This approach is appealing for the advantageous production of high quality MoS2 flakes and their application in biomedicine and biosensing. Moreover, this method can be applied to different starting materials, making the denatured lysozyme a promising bio-tool for surface functionalization of 2D materials., ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). The Nanobiosensors and Bioelectronics Group acknowledges the support from the Generalitat de Cataluña (Grant 2014 SGR 260).

Eumelanins, the dark variant of skin pigments, are endowed with a remarkable antioxidant activity and well-recognized photoprotective properties that have been ascribed to pigment components derived from the biosynthetic precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Herein, we report the protective effect of a polymer obtained starting from the methyl ester of DHICA (MeDHICA-melanin) against Ultraviolet A (UVA)-induced oxidative stress in immortalized human keratinocytes (HaCaT). MeDHICA-melanin was prepared by aerial oxidation of MeDHICA. At concentrations as low as 10 µg/mL, MeDHICA-melanin prevented reactive oxygen species accumulation and partially reduced glutathione oxidation in UVA-irradiated keratinocytes. Western blot experiments revealed that the polymer is able to induce the translocation of nuclear factor erythroid 2–related factor 2 (Nrf-2) to the nucleus with the activation of the transcription of antioxidant enzymes, such as heme-oxygenase 1. Spectrophotometric and HPLC analysis of cell lysate allowed to conclude that a significant fraction (ca. 7%), consisting mainly of the 4,4′-dimer of MeDHICA (ca. 2 μM), was internalized in the cells. Overall these data point to the potential use of MeDHICA-melanin as an antioxidant for the treatment of skin damage, photoaging and skin cancers.

The plants from genus Salvia, as one of the largest genus in Lamiaceae family, are frequently in use for various purposes, as foods, in cosmetic industry, or in traditional and official medicine. Salvia verticillata L. (liliac sage) is one of sidelined sage species with potential bioactivity, reported in traditional medicine. The aim of this study was to acquire a phytochemical profile of the methanol extract obtained from S. verticillata aerial parts and to evaluate its antioxidant, antimicrobial, and biocompatibility potential. Characteristic compounds of the genus Salvia, such as rosmarinic and caffeic acids, along with their derivatives (e.g. salvianolic and yunnaneic acids isomers) and flavonoids, have been identified by ultrahigh-performance Orbitrap metabolomic fingerprinting as the main phenolic metabolites in S. verticillata. The extract displayed moderate antimicrobial properties and significant antioxidant potential, with the half maximal inhibitory concentration values (IC50) ranging from 33 to 73 μg/mL. Importantly, full biocompatibility of the extract with eukaryotic cell lines was observed up to 72 h. The obtained results revealed the presence of polyphenolic bioactive compounds in S. verticillata extract with promising antioxidant potential and significant biocompatibility. In this regard, S. verticillata can find new perspectives of application as a food ingredient, in cosmetic and pharmaceutical industries, as it represents a valuable source of compounds with prominent health properties, with a special focus on rosmarinic acid.

Galdieria phlegrea is a polyextremophilic red alga belonging to Cyanidiophyceae. Galdieria phlegrea C-phycocyanin (GpPC), an abundant light-harvesting pigment with an important role in energy capture and transfer to photosystems, is the C-phycocyanin (C-PC) with the highest thermal stability described so far. GpPC also presents interesting antioxidant and anticancer activities. The X-ray structure of the protein was here solved. GpPC is a [(αβ)3]2 hexamer, with the phycocyanobilin chromophore attached to Cys84α, Cys82β and Cys153β. Details of geometry and interaction with solvent of the chromophores are reported. Comparison with the structure of a C-PC in the entire Porphyridium purpureum phycobilisome system reveals that linker polypeptides have a significant effect on the local structure of the chromophores environment. Comparative analyses with the structures of other purified C-PCs, which were carried out including re-refined models of G. sulphuraria C-PC, reveal that GpPC presents a significantly higher number of inter-trimer salt bridges. Notably, the higher number of salt bridges at the (αβ)3/(αβ)3 interface is not due to an increased number of charged residues in this region, but to subtle conformational variations of their side chains, which are the result of mutations of close polar and non-polar residues.

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)&ndash, Au(I) dinuclear complexes were synthesized, they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)&ndash, Au(I) complex not functionalized with carbohydrates.