A Comparative Study of the Chemical Composition by SPME-GC/MS and Antiradical Activity of Less Common Citrus Species

Citrus secondary metabolites, such as terpene compounds, are very important for human health due to their bioactivity including anti-inflammatory, anti-cancer, and antioxidant effects. In this work, for the first time, the volatile chemical composition of peels and juices from four different Citrus species (C. junos, Citrus × aurantium, C. aurantium ‘Bizzarria’ and C. medica ‘Florentina’, commonly known as Yuzu jeune, Oni Yuzu, Bizzarria orange and Florence cedar, respectively) was investigated by Solid-Phase Microextraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS) technique and the antiradical activity was also examined. The results showed that limonene and γ-terpinene were the main volatile substances detected both in the juices and in the peels, followed by other minority compounds responsible for the phyto-complex of the unique aromas which characterize each individual analyzed Citrus species. Principal component analysis (PCA), performed on volatile compounds, showed both some correlation as well as a clear separation between the juice and the peel of each species. Among them, Oni Yuzu juice was found to be the richest in total polyphenols and flavonoids while its capacity to scavenge ABTS^•+ and DPPH^• radicals was similar to that of Yuzu Jeune and Bizzarria orange.     

Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.1^2,5]decane (compounds 20–23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.0^3,8]decane (compounds 24–27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.     

Temperature effects on the IR absorption bands of hydroxyl and deuteroxyl groups in silica glass

In this report we will show the changes of the band shape of the hydroxyl group (SiOH) infrared (IR) absorption band (～3670 cm^?1) in silica glass induced by lowering temperature in the range from 290 to 20 K. This band is considered as the overlap of several spectral components associated to the vibrational activity of hydroxyl groups in different bond configurations. By a suitable analysis of the experimental band profile in terms of different sub-bands, we studied the thermal evolution of each component and we reconsidered their assignations. For comparison we examined the SiOD absorption band (～2710 cm^?1) as a function of temperature as well. Our data can be interpreted as an evidence of a conversion process of free into H(D)-bonded SiOH(D) groups. Moreover, we estimated the ratio between the molar extinction coefficients of the two main species involved in this process finding that this ratio is appreciably influenced by the isotopic exchange.     

Effects of Bilateral Subthalamic Nucleus Stimulation and Medication on Parkinsonian Speech Impairment

This study aimed to assess quantitatively the effect of bilateral subthalamic nucleus (STN) stimulation and medication on hypokinetic parkinsonian dysarthria. Twelve Italian patients (11 males and 1 female) with idiopathic Parkinson's disease (mean age 60.29+/-7.50 years) and bilateral STN implantation were studied. Neurological assessments and acoustic recordings were performed in four clinical conditions combining stimulation and medication to assess the degree of motor disabilities and speech impairment. Acoustic analysis was performed by means of the Multidimensional Voice Program and the Advanced Motor Speech Profile (Kay Elemetrics, Lincoln Park, NJ). None of the evaluated parameters deteriorated after STN deep brain stimulation. STN stimulation significantly improved motor performances and vocal tremor and provided a major stability to glottal vibration. Effect of stimulation on these parameters was superior to that of levodopa. No significant variations were observed in perceptual evaluation and in acoustic parameters related to prosody, articulation, and intensity after either stimulation or medication. The improvement of acoustic parameters related to glottal vibration and voice tremor was not accompanied by a substantial effect on speech intelligibility. STN stimulation was more effective on global motor limb dysfunctions than on dysarthria, but we did not report negative consequences on speech.     

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.     

Natural Cryoprotective and Cytoprotective Agents in Cryopreservation: A Focus on Melatonin

Cryoprotective and cytoprotective agents (Cytoprotective Agents) are fundamental components of the cryopreservation process. This review presents the essentials of the cryopreservation process by examining its drawbacks and the role of cytoprotective agents in protecting cell physiology. Natural cryoprotective and cytoprotective agents, such as antifreeze proteins, sugars and natural deep eutectic systems, have been compared with synthetic ones, addressing their mechanisms of action and efficacy of protection. The final part of this article focuses melatonin, a hormonal substance with antioxidant properties, and its emerging role as a cytoprotective agent for somatic cells and gametes, including ovarian tissue, spermatozoa and spermatogonial stem cells.     

Pathophysiological Role and Medicinal Chemistry of A2A Adenosine Receptor Antagonists in Alzheimer’s Disease

The A_2A adenosine receptor is a protein belonging to a family of four GPCR adenosine receptors. It is involved in the regulation of several pathophysiological conditions in both the central nervous system and periphery. In the brain, its localization at pre- and postsynaptic level in striatum, cortex, hippocampus and its effects on glutamate release, microglia and astrocyte activation account for a crucial role in neurodegenerative diseases, including Alzheimer’s disease (AD). This ailment is considered the main form of dementia and is expected to exponentially increase in coming years. The pathological tracts of AD include amyloid peptide-β extracellular accumulation and tau hyperphosphorylation, causing neuronal cell death, cognitive deficit, and memory loss. Interestingly, in vitro and in vivo studies have demonstrated that A_2A adenosine receptor antagonists may counteract each of these clinical signs, representing an important new strategy to fight a disease for which unfortunately only symptomatic drugs are available. This review offers a brief overview of the biological effects mediated by A_2A adenosine receptors in AD animal and human studies and reports the state of the art of A_2A adenosine receptor antagonists currently in clinical trials. As an original approach, it focuses on the crucial role of pharmacokinetics and ability to pass the blood–brain barrier in the discovery of new agents for treating CNS disorders. Considering that A_2A receptor antagonist istradefylline is already commercially available for Parkinson’s disease treatment, if the proof of concept of these ligands in AD is confirmed and reinforced, it will be easier to offer a new hope for AD patients.     

Detection of Volatiles by HS-SPME-GC/MS and Biological Effect Evaluation of Buddha’s Hand Fruit

The present work aimed to chemically characterize and evaluate the antiradical power and biological effects of Citrus medica var. sarcodactylus essential oil (EO) and hydrolate (Hy) from exocarp as well as methanol extracts, from both exocarp and mesocarp (EEX and MEX). The whole fresh fruit was also investigated by SPME-GC/MS to describe its volatile composition. EO and Hy were analyzed by GC/MS and HS-GC/MS techniques, respectively. Limonene and γ-terpinene were found to be the most abundant compounds both in the fresh parts of the fruit and in the EO, while α-terpineol and terpinen-4-ol were in the Hy. The extracts were also rich in furan and coumarin derivatives. A good antiradical activity of all samples except Hy was detected both against ABTS·+ than DPPH·, removed up to about 50%. The antibacterial activity against Bacillus cereus and Escherichia coli was evaluated by microwell dilution method to determine MIC and MBC values. EEX and MEX showed efficacy at very high concentrations against both tested bacteria. The MIC value of EO against B. cereus was 0.5% v/v, while Hy was not able to inhibit the bacterial growth at the tested concentrations. Cytotoxicity investigated on the HL60 leukemia cell line by MTT assay provided an EC₅₀ of 1.24% v/v for EO. Interesting activity of Hy was also observed.     

Development of an LC–DAD–MS-Based Method for the Analysis of Hydroxyanthracene Derivatives in Food Supplements and Plant Materials

Products based on plants containing hydroxyanthracene derivatives (HADs)—such as Rheum, Cassia, and Aloe species—are widely used in food supplements or nutraceuticals due to their laxative effects. A more restricted control of HAD contents in food supplements has been implemented by EU Regulation 2021/468, in order to increase the safety of these preparations. Due to their toxicity, aloin A, aloin B, aloe emodin, emodin, and the synthetic derivative danthron have been listed as prohibited substances in food supplements, being tolerated in amounts < 1 mg kg⁻¹ in marketed products. In this work, we report the development of a sensitive and fast LC–DAD–MS-based procedure for the determination of these five compounds in food supplements and plant materials or extracts. The entire procedure includes a simple sample preparation step, where target analytes are concentrated by means of solvent extraction and evaporative concentration (solid samples), or by lyophilisation (liquid samples). The average LOQ of 0.10 mg/L, LOD of 0.03 mg/L, accuracy, and precision with CVs below 12.72 were obtained for the studied analytes. This method is suitable for assessing the compliance of commercial products and raw materials with EU Regulation 2021/468. Furthermore, the proposed method can represent a starting point for the development of a unique and standardised analytical approach for the determination of other HADs under the attention of EU authorities.     

Carbocation catalysis in confined space: activation of trityl chloride inside the hexameric resorcinarene capsule

Carbocation catalysis can be performed inside the confined space of the hexameric resorcinarene capsule. The inner cavity of the capsule can host the trityl carbocation, which catalyses the Diels–Alder reaction between dienes and unsaturated aldehydes. Experimental results and in silico calculations show that the hexameric resorcinarene capsule C₆ can promote the formation of the trityl carbocation from trityl chloride through the cleavage of the carbon–halogen bond promoted by OH⋯X⁻ hydrogen bonding. Here it is shown that the combination of the nanoconfined space and the latent carbocation catalysis provides a convenient complementary strategy for the typical carbocation catalysis. The latent strategy bypasses the typical pitfalls associated with active carbocations and provides control of the reaction efficiency in terms of reaction rate, conversion, and selectivity.

The hexameric resorcinarene capsule is able to promote carbocation catalysis inside its cavity.