Synthesis and Biological Evaluation of Halogenated E-Stilbenols as Promising Antiaging Agents

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations of reactive oxygen species. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RSV) plays a critical role in slowing the aging process but has a poor bioavailabity after oral intake. In this present work, a series of RSV derivatives was designed, synthesized, and evaluated as potential antioxidant agents. These derivatives contain substituents with different electronic and steric properties in different positions of aromatic rings. This kind of substituents affects the activity and the bioavailability of these compounds compared with RSV used as reference compound. Studies of Log P values demonstrated that the introduction of halogens gives the optimum lipophilicity to be considered promising active agents. Among them, compound 6 showed the higher antioxidant activity than RSV. The presence of trifluoromethyl group together with a chlorine atom increased the antioxidant activity compared to RSV.     

High yield synthesis of 4H‐1,4‐benzothiazine‐1,1‐dioxide derivatives

4H‐1,4‐Benzothiazine‐1,1‐dioxide derivatives were synthesized through a sequence of almost quantitative reactions. The commercial starting material 2‐(methylsulfanyl)aniline was Boc‐protected, N‐acylated and oxidized at the sulfur atom to obtain a sulfonyl derivative. An anionic transposition of the acyl group followed by asimultaneous deprotection‐cyclization gave the title products in excellent yields. All products and intermediates were fully characterized.     

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.     

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations—up to 300 μM, corresponding to ca. 50% of the overall content—were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.     

The Different Facets of Triclocarban: A Review

In the late 1930s and early 1940s, it was discovered that the substitution on aromatic rings of hydrogen atoms with chlorine yielded a novel chemistry of antimicrobials. However, within a few years, many of these compounds and formulations showed adverse effects, including human toxicity, ecotoxicity, and unwanted environmental persistence and bioaccumulation, quickly leading to regulatory bans and phase-outs. Among these, the triclocarban, a polychlorinated aromatic antimicrobial agent, was employed as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies, and especially of personal care products, such as soaps, toothpaste, and shampoo. Triclocarban has been widely used for over 50 years, but only recently some concerns were raised about its endocrine disruptive properties. In September 2016, the U.S. Food and Drug Administration banned its use in over-the-counter hand and body washes because of its toxicity. The withdrawal of triclocarban has prompted the efforts to search for new antimicrobial compounds and several analogues of triclocarban have also been studied. In this review, an examination of different facets of triclocarban and its analogues will be analyzed.     

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.     

Octapalladium Strings Trap C60 and C70 Fullerenes Affording Metal-Chain-Wired Bucky Balls

Reactions of Pd₈ strings supported by meso-Ph₂PCH₂P(Ph)CH₂P(Ph)CH₂PPh₂ (meso-dpmppm) ligands, [Pd₈(meso-dpmppm)₄(L)₂]⁴⁺ (L=CH₃CN ( 1 ), XylNC ( 2 )) with C₆₀ resulted in the exclusive formation of unprecedented metal-chain-wired C₆₀ bucky balls, [{Pd₄(meso-dpmppm)₂(L)}₂(C₆₀)]⁴⁺ (L=CH₃CN ( 11 ), XylNC ( 12 )), in which a C₆₀ fullerene is trapped in the central Pd–Pd junction, as unambiguously established by spectroscopic, X-ray crystallographic, and theoretical techniques. The similar reaction of Pd₈ strings supported by rac-dpmppm, [Pd₈(rac-dpmppm)₄(CH₃CN)₂]⁴⁺ ( 3 ) also afforded a racemic mixture of [{Pd₄((R*,R*)-dpmppm)₂(CH₃CN)}₂(C₆₀)]⁴⁺ ( 13 ) without scrambling the Pd₄ fragments with (R,R)- and (S,S)-dpmppm ligands. Consequently, those of enantiopure chiral Pd₈ strings, [Pd₈((R*,R*)-dpmppm)₄(CH₃CN)₂]⁴⁺, certainly afforded chiral bucky balls of [{Pd₄((R*,R*)-dpmppm)₂(CH₃CN)}₂(C₆₀)]⁴⁺ ( 13 _RR and 13 _SS ), that exhibit mirror-image circular dichroism spectra. The reactions of 1 and 2 were also applied for trapping a C₇₀ fullerene to give 2 : 1 adducts of [{Pd₄(meso-dpmppm)₂(L)}₂(C₇₀)]⁴⁺ (L=CH₃CN ( 21 ), XylNC ( 22 )). These results provide useful information for creating a platform to develop dimensionally and chirality controlled metal–carbon nanocomposite materials.     

Plans for implementation of a quality system in the control laboratory of the Romanian National Medicines Agency

This paper describes the practical implementation of a quality system in the control laboratory of the National Medicines Agency, Romania, the main aim being the alignment of the requirements of the control of drugs in Romania with European Union standards. Activity in this field is relatively new in Romania, however, it is of great importance to Romania’s compliance with international standards. Received: 13 September 2000 Accepted: 19 February 2001     

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy.     

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.