Thiol-functionalized cellulose for mercury polluted water remediation: Synthesis and study of the adsorption properties.

Mercury pollution poses a global health threat due to its high toxicity, especially in seafood where it accumulates through various pathways. Developing effective and affordable technologies for mercury removal from water is crucial. Adsorption stands out as a promising method, but creating low-cost materials with high selectivity and capacity for mercury adsorption is challenging. Here we show a sustainable method to synthesize low-cost sulfhydrylated cellulose with ethylene sulfide functionalities bonded glucose units. Thiol-functionalized cellulose exhibits exceptional adsorption capacity (1325 mg g-1) and selectivity for Hg(II) over other heavy metals (Co, Cu, Zn, Pb) and common cations (Ca++, Mg++) found in natural waters. It performs efficiently across a wide pH range and different aqueous matrices, including wastewater, and can be regenerated and reused multiple times without significant loss of performance. This approach offers a promising solution for addressing mercury contamination in water sources.

1,2,3-Triazole Hybrids Containing Isatins and Phenolic Moieties: Regioselective Synthesis and Molecular Docking Studies.

The synthesis of hybrid molecules is one of the current strategies of drug discovery for the development of new lead compounds. The 1,2,3-triazole moiety represents an important building block in Medicinal Chemistry, extensively present in recent years. In this paper, we presented the design and the synthesis of new 1,2,3-triazole hybrids, containing both an isatine and a phenolic core. Firstly, the non-commercial azide and the alkyne synthons were prepared by different isatines and phenolic acids, respectively. Then, the highly regioselective synthesis of 1,4-disubstituted triazoles was obtained in excellent yields by a click chemistry approach, catalyzed by Cu(I). Finally, a molecular docking study was performed on the hybrid library, finding four different therapeutic targets. Among them, the most promising results were obtained on 5-lipoxygenase, an enzyme involved in the inflammatory processes.

Reactive Deep Eutectic Solvent for an Eco-Friendly Synthesis of Cellulose Carbamate.

The limited solubility of natural cellulose in water and common organic solvents hinders its diverse applications, despite being one of the most abundant and easily accessible biopolymers on Earth. Chemical derivatization, such as cellulose carbamate (CC), offers a pathway to enhance both solubility and industrial processability. In this study, CC was synthesized by exploiting a novel type IV deep eutectic solvent (DES) composed of erbium trichloride and urea. This DES was shown to be not only an environmentally friendly reaction medium/catalyst but also actively participated in the synthetic process as a reagent. The resultant cellulose carbamate samples were characterized through FT-IR and elemental analysis. A nitrogen content value of 1.59% was afforded determining a degree of substitution corresponding to a value of 0.19. One of the key scientific advancements lies in the preparation of cellulose carbamate using a straightforward and cost-effective method. This approach utilizes non-toxic compounds, aligning with the principles of green chemistry and contributing to sustainable development in cellulose derivative production.

Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells.

Naringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The F1FO-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especially in the presence of Ca2+ cation used as cofactor. Indeed, NRG was a selective inhibitor of the hydrophilic F1 domain displaying a binding site overlapped with quercetin in the inside surface of an annulus made by the three α and the three ß subunits arranged alternatively in a hexamer. The kinetic constant of inhibition suggested that NRG preferred the enzyme activated by Ca2+ rather than the F1FO-ATPase activated by the natural cofactor Mg2+. From the inhibition type mechanism of NRG stemmed the possibility to speculate that NRG can prevent the activation of F1FO-ATPase by Ca2+. The event correlated to the protective role in the mitochondrial permeability transition pore opening by NRG as well as to the reduction of ROS production probably linked to the NRG chemical structure with antioxidant action. Moreover, in primary cerebral endothelial cells (ECs) obtained from stroke prone spontaneously hypertensive rats NRG had a protective effect on salt-induced injury by restoring cell viability and endothelial cell tube formation while also rescuing complex I activity.

Highly Diastereoselective Multicomponent Synthesis of Spirocyclopropyl Oxindoles Enabled by Rare-Earth Metal Salts.

The synthesis of polysubstituted spirocyclopropyl oxindoles using a series of rare-earth metal (REM) salts is reported. REMs, in particular Sc(OTf)3, allowed access to the target compounds by a multicomponent reaction with high diastereoselectivity (≤94:6:0:0). Density functional theory calculations on the model reaction are consistent with the observed selectivity and revealed that the special coordinating capabilities and the oxophilicity of the metal are key factors in inducing the formation of one main diastereoisomer.

Bio-Based Polyurethane Foams for the Removal of Petroleum-Derived Pollutants: Sorption in Batch and in Continuous-Flow.

In this paper, we evaluated the potential of two synthesized bio-based polyurethane foams, PU1 and PU2, for the removal of diesel and gasoline from water mixtures. We started the investigation with the experiment in batch. The total sorption capacity S (g/g) for the diesel/water system was slightly higher with respect to gasoline/water, with a value of 62 g/g for PU1 and 65 g/g for PU2. We found that the sorption follows a pseudo second-order kinetic model for both the materials. The experimental data showed that the best isotherm models were obtained with Langmuir and Redlich-Peterson models. In addition, to provide an idea of the process scalability for future industrial applications, we tested the sorption capacity of the foams using a continuous-flow of the same oil/water mixtures and we obtained performances even better with respect to the batch test. The regeneration can be performed up to 50 times by centrifuge, without losing efficacy.

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation.

An efficient, eco-compatible, and very cheap method for the construction of fully substituted pyrazoles (Pzs) via eliminative nitrilimine-alkene 1,3-dipolar cycloaddition (ENAC) reaction was developed in excellent yield and high regioselectivity. Enaminones and nitrilimines generated in situ were selected as dipolarophiles and dipoles, respectively. A deep screening of the employed base, solvent, and temperature was carried out to optimize reaction conditions. Recycling tests of ionic liquid were performed, furnishing efficient performance until six cycles. Finally, a plausible mechanism of cycloaddition was proposed. Then, the effect of three different structures of Pzs was evaluated on the F1FO-ATPase activity and mitochondrial permeability transition pore (mPTP) opening. The Pz derivatives' titration curves of 6a, 6h, and 6o on the F1FO-ATPase showed a reduced activity of 86%, 35%, and 31%, respectively. Enzyme inhibition analysis depicted an uncompetitive mechanism with the typical formation of the tertiary complex enzyme-substrate-inhibitor (ESI). The dissociation constant of the ESI complex (Ki') in the presence of the 6a had a lower order of magnitude than other Pzs. The pyrazole core might set the specific mechanism of inhibition with the F1FO-ATPase, whereas specific functional groups of Pzs might modulate the binding affinity. The mPTP opening decreased in Pz-treated mitochondria and the Pzs' inhibitory effect on the mPTP was concentration-dependent with 6a and 6o. Indeed, the mPTP was more efficiently blocked with 0.1 mM 6a than with 1 mM 6a. On the contrary, 1 mM 6o had stronger desensitization of mPTP formation than 0.1 mM 6o. The F1FO-ATPase is a target of Pzs blocking mPTP formation.

1,5-disubstituted-1,2,3-triazoles counteract mitochondrial dysfunction acting on F1FO-ATPase in models of cardiovascular diseases.

The compromised viability and function of cardiovascular cells are rescued by small molecules of triazole derivatives (Tzs), identified as 3a and 3b, by preventing mitochondrial dysfunction. The oxidative phosphorylation improves the respiratory control rate in the presence of Tzs independently of the substrates that energize the mitochondria. The F1FO-ATPase, the main candidate in mitochondrial permeability transition pore (mPTP) formation, is the biological target of Tzs and hydrophilic F1 domain of the enzyme is depicted as the binding region of Tzs. The protective effect of Tz molecules on isolated mitochondria was corroborated by immortalized cardiomyocytes results. Indeed, mPTP opening was attenuated in response to ionomycin. Consequently, increased mitochondrial roundness and reduction of both length and interconnections between mitochondria. In in-vitro and ex-vivo models of cardiovascular pathologies (i.e., hypoxia-reoxygenation and hypertension) were used to evaluate the Tzs cardioprotective action. Key parameters of porcine aortic endothelial cells (pAECs) oxidative metabolism and cell viability were not affected by Tzs. However, in the presence of either 1 µM 3a or 0.5 µM 3b the impaired cell metabolism of pAECs injured by hypoxia-reoxygenation was restored to control respiratory profile. Moreover, endothelial cells isolated from SHRSP exposed to high-salt treatment rescued the Complex I activity and the endothelial capability to form vessel-like tubes and vascular function in presence of Tzs. As a result, the specific biochemical mechanism of Tzs to block Ca2+-activated F1FO-ATPase protected cell viability and preserved the pAECs bioenergetic metabolism upon hypoxia-reoxygenation injury. Moreover, SHRSP improved vascular dysfunction in response to a high-salt treatment.

Regioselective Synthesis and Molecular Docking Studies of 1,5-Disubstituted 1,2,3-Triazole Derivatives of Pyrimidine Nucleobases.

1,2,3-triazoles are versatile building blocks with growing interest in medicinal chemistry. For this reason, organic chemistry focuses on the development of new synthetic pathways to obtain 1,2,3-triazole derivatives, especially with pyridine moieties. In this work, a novel series of 1,5-disubstituted-1,2,3-triazoles functionalized with pyrimidine nucleobases were prepared via 1,3-dipolar cycloaddition reaction in a regioselective manner for the first time. The N1-propargyl nucleobases, used as an alkyne intermediate, were obtained in high yields (87-92%) with a new two-step procedure that selectively led to the monoalkylated compounds. Then, FeCl3 was employed as an efficient Lewis acid catalyst for 1,3-dipolar cycloaddition between different aryl and benzyl azides and the N1-propargyl nucleobases previously synthesized. This new protocol allows the synthesis of a series of new 1,2,3-triazole derivatives with good to excellent yields (82-92%). The ADME (Absorption, Distribution, Metabolism, and Excretion) analysis showed good pharmacokinetic properties and no violations of Lipinsky's rules, suggesting an appropriate drug likeness for these new compounds. Molecular docking simulations, conducted on different targets, revealed that two of these new hybrids could be potential ligands for viral and bacterial protein receptors such as human norovirus capsid protein, SARS-CoV-2 NSP13 helicase, and metallo-ß-lactamase.

Biochar-Supported TiO2-Based Nanocomposites for the Photocatalytic Degradation of Sulfamethoxazole in Water-A Review.

Sulfamethoxazole (SMX) is a frequently used antibiotic for the treatment of urinary tract, respiratory, and intestinal infections and as a supplement in livestock or fishery farming to boost production. The release of SMX into the environment can lead to the development of antibiotic resistance among the microbial community, which can lead to frequent clinical infections. SMX removal from water is usually done through advanced treatment processes, such as adsorption, photocatalytic oxidation, and biodegradation. Among them, the advanced oxidation process using TiO2 and its composites is being widely used. TiO2 is a widely used photocatalyst; however, it has certain limitations, such as low visible light response and quick recombination of e-/h+ pairs. Integrating the biochar with TiO2 nanoparticles can overcome such limitations. The biochar-supported TiO2 composites showed a significant increase in the photocatalytic activities in the UV-visible range, which resulted in a substantial increase in the degradation of SMX in water. The present review has critically reviewed the methods of biochar TiO2 composite synthesis, the effect of biochar integration with the TiO2 on its physicochemical properties, and the chemical pathways through which the biochar/TiO2 composite degrades the SMX in water or aqueous solution. The degradation of SMX using photocatalysis can be considered a useful model, and the research studies presented in this review will allow extending this area of research on other types of similar pharmaceuticals or pollutants in general in the future.

Synthesis, Characterization and Mechanical Properties of Novel Bio-Based Polyurethane Foams Using Cellulose-Derived Polyol for Chain Extension and Cellulose Citrate as a Thickener Additive.

A novel series of bio-based polyurethane composite foams was prepared, employing a cellulose-derived polyol for chain extension and cellulose-citrate as a thickener additive. The utilized polyol was obtained from the reduction reaction of cellulose-derived bio-oil through the use of sodium borohydride and iodine. Primarily, we produced both rigid and flexible polyurethane foams through chain extension of the prepolymers. Secondly, we investigated the role of cellulose citrate as a polyurethane additive to improve the mechanical properties of the realized composite materials. The products were characterized by FT-IR spectroscopy and their morphologies were analysed by SEM. Mechanical tests were evaluated to open new perspectives towards different applications.

Efficient and Fast Removal of Oils from Water Surfaces via Highly Oleophilic Polyurethane Composites.

In this study we evaluated the oil adsorption capacity of an aliphatic polyurethane foam (PU 1) and two of its composites, produced through surface coating using microparticles of silica (PU-Si 2) and activated carbon (PU-ac 3). The oil adsorption capacity in diesel was improved up to 36% using the composite with silica and up to 50% using the composite with activated carbon with respect to the initial PU 1. Excellent performances were retained in gasoline and motor oil. The adsorption was complete after a few seconds. The process follows a monolayer adsorption fitted by the Langmuir isotherm, with a maximum adsorption capacity of 29.50 g/g of diesel for the composite with activated carbon (PU-ac 3). These materials were proved to be highly oleophilic for oil removal from fresh water and sea water samples. Regeneration and reuse can be repeated up to 50 times by centrifugation, without a significant loss in adsorption capacity.

Cellulose citrate: a convenient and reusable bio-adsorbent for effective removal of methylene blue dye from artificially contaminated water.

In the present work, we proved the efficacy of cellulose citrate to remove methylene blue (MB) from artificially contaminated water. MB is a widely used dye, but because of its chemical aromatic structure, it is significantly stable with quite slow biodegradation, causing consequent serious health problems for people and significant environmental pollution. Cellulose citrate, the bio-adsorbent proposed and studied by us to remediate water polluted by MB, is produced by a green, cheap and fast procedure that makes use of two abundant natural products, cellulose and citric acid. The average of two citrate groups for each glucose unit of cellulose chains allows this material to have many carboxylic groups available for interaction with the cationic dye. The characterization was carried out through FT-IR, SEM, specific surface area, pore structure parameters and zeta potential. The negative value of the zeta potential at neutral pH is consistent with the affinity of this material for the adsorption of cationic compounds like MB. The activity of the adsorbent at different times, temperatures, pH and concentrations was investigated. The process followed monolayer adsorption typical of the Langmuir model, with a maximum adsorption capacity of 96.2 mg g-1, while for the kinetic studies the process followed a pseudo-second order model. The highest levels of adsorption were reported using solutions of dye with concentrations under 100 mg L-1. The adsorbent can be regenerated several times without a significant loss in the adsorption capacity, and it is not strongly affected by temperature and pH, giving rise to a simple and eco-sustainable procedure for water remediation. Therefore, we conclude that cellulose citrate can be considered as a promising bio-adsorbent for the removal of MB and other cationic pollutants from the environment.

1,5-Disubstituted-1,2,3-triazoles as inhibitors of the mitochondrial Ca2+ -activated F1 FO -ATP(hydrol)ase and the permeability transition pore.

The mitochondrial permeability transition pore (mPTP), a high-conductance channel triggered by a sudden Ca2+ concentration increase, is composed of the F1 FO -ATPase. Since mPTP opening leads to mitochondrial dysfunction, which is a feature of many diseases, a great pharmacological challenge is to find mPTP modulators. In our study, the effects of two 1,5-disubstituted 1,2,3-triazole derivatives, five-membered heterocycles with three nitrogen atoms in the ring and capable of forming secondary interactions with proteins, were investigated. Compounds 3a and 3b were selected among a wide range of structurally related compounds because of their chemical properties and effectiveness in preliminary studies. In swine heart mitochondria, both compounds inhibit Ca2+ -activated F1 FO -ATPase without affecting F-ATPase activity sustained by the natural cofactor Mg2+ . The inhibition is mutually exclusive, probably because of their shared enzyme site, and uncompetitive with respect to the ATP substrate, since they only bind to the enzyme-ATP complex. Both compounds show the same inhibition constant (K'i ), but compound 3a has a doubled inactivation rate constant compared with compound 3b. Moreover, both compounds desensitize mPTP opening without altering mitochondrial respiration. The results strengthen the link between Ca2+ -activated F1 FO -ATPase and mPTP and suggest that these inhibitors can be pharmacologically exploited to counteract mPTP-related diseases.

"We have already heard that the treatment doesn't do anything, so why should we take it?": A mixed method perspective on Chagas disease knowledge, attitudes, prevention, and treatment behaviour in the Bolivian Chaco.

BACKGROUND: Chagas disease (CD) is highly endemic in the Bolivian Chaco. The municipality of Monteagudo has been targeted by national interventions as well as by Médecins Sans Frontières to reduce infection rates, and to decentralize early diagnosis and treatment. This study seeks to determine the knowledge and attitudes of a population with increased awareness and to identify remaining factors and barriers for sustained vector control, health care seeking behaviour, and access, in order to improve future interventions. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted among approximately 10% (n = 669) of the municipality of Monteagudo's households that were randomly selected. Additionally, a total of 14 in-depth interviews and 2 focus group discussions were conducted with patients and key informants. Several attitudes and practices were identified that could undermine effective control against (re-)infection. Knowledge of clinical symptoms and secondary prevention was limited, and revealed specific misconceptions. Although 76% of the participants had been tested for CD, only 18% of those who tested positive concluded treatment with benznidazole (BNZ). Sustained positive serologies after treatment led to perceived ineffectiveness of BNZ. Moreover, access barriers such as direct as well as indirect costs, BNZ stock-outs and a fear of adverse reactions triggered by other community members made patients opt for alternative treatments against CD such as veterinary ivermectin, used by 28% of infected participants in our study. The lack of accessible care for chronic complications as well as socioeconomic consequences, such as the exclusion from both job opportunities and bank loans contributed to the ongoing burden of CD. CONCLUSIONS/SIGNIFICANCE: Large scale interventions should be accompanied by operational research in order to identify misconceptions and unintended consequences early on, to generate accessible data for future interventions, and for rigorous evaluation. An integrated, community-based approach tackling social determinants and including both traditional and animal health sectors might help to overcome current barriers and advocate for patients' rights.

Sequestering Ability of a Synthetic Chelating Agent towards Copper(II) and Iron(III): A Detailed Theoretical and Experimental Analysis.

In the continuous effort to identify selective chelators towards bioavailable and toxic metal ions, the potential selectivity of a novel N,O chelating ligand, recently synthesized and claimed to be able to bind to Cu(II) ions forming stable complexes while leaving unaltered the level of essential metal ions, was scrutinized using a combined theoretical and experimental approach. A multistep synthetic procedure was used to synthesize the ligand, whose chelating properties along with the stability of the complexes formed binding Cu(II) and, for comparison, Fe(III) ions were evaluated using potentiometric measurements and UV-Vis spectroscopy. DFT analysis allowed to disclose the structural characteristics of the formed complexes. In the plethora of all the possible structures, a selection of the most reliable ones was achieved by means of a stringent comparison between experimental and simulated UV-Vis spectra. The outcomes of the present investigation demonstrate that the Cu(II) sequestering ability of the ligand is smaller than that towards Fe(III). The strategy used here should allow to check the propensity of ligands in selectively binding metal ions.

Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial.

OBJECTIVES: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE). METHODS: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing. RESULTS: Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL. CONCLUSION: The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate. TRIAL REGISTRATION NUMBER: NCT01649765.

Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial.

OBJECTIVE: The principle of replacing prandial insulin lispro with a once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) for type 2 diabetes inadequately controlled on a multiple daily insulin injections regimen was tested with albiglutide. RESEARCH DESIGN AND METHODS: In this treat-to-target study, basal plus prandial insulin was optimized over 4 weeks before participants were randomized (1:1) to albiglutide plus optimized basal insulin glargine and lispro (dose reduced by 50% at randomization; subsequently, lispro injections were fully discontinued 4 weeks later) (n = 402) or to continued optimized lispro plus optimized glargine (n = 412). RESULTS: Mean ± SD HbA1c at baseline, 7.8 ± 0.6% (61 ± 7 mmol/mol) in the albiglutide + glargine group and 7.7 ± 0.6% (60 ± 7 mmol/mol) in the lispro + glargine group, was reduced at week 26 to 6.7 ± 0.8% (49 ± 8 mmol/mol) and 6.6 ± 0.8% (48 ± 8 mmol/mol), respectively (least squares [LS] difference 0.06% [95% CI -0.05 to 0.17]; noninferiority P < 0.0001). In the albiglutide + glargine group, 218 participants (54%) replaced all prandial insulin without reintroducing lispro up to week 26. Total daily prandial insulin dose was similar at baseline but was lower by 62 units/day (95% CI -65.9 to -57.8; P < 0.0001) at week 26 in the albiglutide + glargine group, and the total number of weekly injections was also reduced from 29 to 13 per week. Less severe/documented symptomatic hypoglycemia (57.2% vs. 75.0%) occurred in the albiglutide + glargine group with meaningful weight differences (LS mean ± SE -2.0 ± 0.2 vs. +2.4 ± 0.2 kg; P < 0.0001) vs. lispro + glargine. Gastrointestinal adverse events were higher with albiglutide + glargine (26% vs. 13%). CONCLUSIONS: A once-weekly GLP-1RA was able to substitute for prandial insulin in 54% of people, substantially reducing the number of prandial insulin injections; glycemic control improved, with the added benefits of weight loss and less hypoglycemia in the GLP-1RA arm. Replacing prandial insulin with a weekly GLP-1RA can simplify basal plus prandial insulin treatments and achieve better outcomes in type 2 diabetes.

Totally green cellulose conversion into bio-oil and cellulose citrate using molten citric acid in an open system: synthesis, characterization and computational investigation of reaction mechanisms.

The simultaneous transformation of crystalline or amorphous cellulose into a furan-based bio-oil and cellulose citrate was realized avoiding the use of strong inorganic acids, drastic conditions, enzymatic treatments or microorganism fermentation. This innovative method is very eco-friendly and involves the use of molten citric acid under solvent free conditions at atmospheric pressure. An accurate discussion on chemical composition of the bio-oil enriched in bioprivileged molecules as well as structural and morphological characterization of cellulose citrate was reported. Moreover, mechanistic hypotheses were formulated on the basis of experimental findings and detailed DFT quantum-mechanical simulations were carried out to confirm, step by step, the proposed reaction paths.

Synthesis, Biological and In Silico Evaluation of Pure Nucleobase-Containing Spiro (Indane-Isoxazolidine) Derivatives as Potential Inhibitors of MDM2-p53 Interaction.

Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1,3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2-p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis.