Crystallization-induced diastereomer transformation assists the diastereoselective synthesis of 4-nitroisoxazolidine scaffolds.

This communication describes a solution to the vexing problem of synthesis of 4-nitroisoxazolidine rings from cyclic nitrones and ß-nitrostyrenes. The trans-endo adduct 2 is quantitatively synthesised from E-ß-nitrostyrene under mild conditions avoiding purification, while the trans-exo adduct 4 is obtained at higher temperatures. Furthermore, a Crystallization-Induced Diastereomer Transformation (CIDT) process was used to epimerise the NO2 bond from 2 to the cis-exo adduct 3 with total conversion assisted by the para-halogen substitution of the aromatic ring without any additives. By combining these approaches, we can establish a simple synthetic methodology that allows the diastereoselective synthesis of three diastereoisomers, overcoming the previous problems described in the literature.

Exploring adolescents' experiences of continuing to wear face masks during COVID-19: A qualitative descriptive study in Barcelona (Spain).

BACKGROUND: The COVID-19 pandemic prompted the use of face masks as a social distancing measure. Although evidence supports their effectiveness in preventing infection, it remains unclear why some adolescents choose to continue wearing them postpandemic, even when it is no longer mandatory. This study aims to explore adolescents' experiences of wearing face masks during the COVID-19 pandemic when their use was no longer mandatory. METHOD: In this exploratory qualitative study, data were collected from 16 adolescents through face-to-face semistructured interviews. The participants were asked about the reasons and feelings associated with continuing to wear masks, as well as the contexts in which they felt safe without a mask. The collected data were analysed using Braun and Clarke's thematic analysis. RESULTS: Three main themes were identified: (1) Navigating complex decision-making: balancing safety and self-image, (2) peer influence dynamics and (3) managing the future: weather dynamics and pandemic evolution. DISCUSSION: The potential implications of withdrawing COVID-19 preventive measures, such as mask-wearing, beyond the pandemic remain understudied. It is crucial to further investigate the perceptions related to wearing masks and its cessation, especially amongst vulnerable individuals. PATIENT OR PUBLIC CONTRIBUTION: Due to methodological constraints associated with participants' age, they were not engaged in the design, data analysis, data interpretation or manuscript preparation phases of the study.

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space.

The concept of bioisostere replacement is of paramount importance in medicinal chemistry, as it can be employed as a rational to expand bioactive chemical space to tackle lead optimization issues like lack of potency, efficacy, and selectivity or pharmacokinetic/dynamic issues. One of the most important building blocks (in the sense of participating in a vast area of chemical space of biological importance) in medicinal chemistry is the 2-phenethyl moiety, a key component of diverse drug-like entities. Although the core 2-phenethylamine structure has been recognized by the drug discovery community, little attention has been given to the various ring-based rescaffolding procedures that can be conducted with this unit. In this regard, a review on the use of 2-heteroarylethylamines displaying pharmacological activity is reported. A detailed description of flexible, amine-opened motifs is provided, that describes therapeutic targets and other potent bioactive examples, which will be a valuable repository of phenyl, heteroaryl, and other replacement units of high value to the drug discovery community.

Erythema nodosum after COVID-19 vaccine: Report of two pediatric cases.

With the introduction of large-scale COVID-19 vaccination programs, a variety of cutaneous manifestations have been described. We present two girls (ages 12 and 5 years) who developed erythema nodosum (EN) 3 and 14 days after Pfizer-BioNTech COVID-19 vaccination, respectively. While EN after COVID-19 vaccination has been reported in adults, it is can also occur in children.

2-Phenethylamines in Medicinal Chemistry: A Review.

A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this motif are enumerated in key therapeutic targets, listing medicinal chemistry hits and appealing screening compounds. Latest reports in discovering new bioactive 2-phenethylamines by research groups are covered too.

The Impact of COVID-19 on Adolescents' Mental Health in Catalonia (Spain): A Qualitative Study.

This study aimed to understand the experiences of adolescents regarding the perceived impact of COVID-19 on their mental health in Catalonia (Spain). A qualitative exploratory methodology was used with a purposive sample of 30 high-school students regarding their experiences of the self-perceived impact of COVID-19 on their mental health. Data were thematically analyzed using Braun and Clarke method. Three main themes emerged from the data: (a) the challenge of living confined, (b) the footprint of COVID-19 on adolescents' mental health, and (c) school dynamics during the lockdown. The COVID-19 pandemic negatively impacted adolescents' mental health, and adolescents perceived a lack of emotional support from educational centers. Therefore, incorporating emotional support in educational centers and offering emotional self-management tools to young students should be a priority. School nurses can play an essential role in recognizing and managing emotional needs and being the natural link between educational and primary care centers.

Apremilast and biologics: Characteristics of patients treated with apremilast before, during, or after a biological treatment.

Apremilast is an oral small molecule approved for the treatment of psoriasis, psoriatic arthritis and oral ulcers associated with Behçet's disease. This research was conducted to describe the characteristics of patients who received treatment with apremilast for a skin disorder, either before, during, or after a biological treatment, with the aim of analyze the reasons that lead to start this drug in real clinical practice or suspend it for another. A total of 41 patients were enrolled: nine (22.0%) had received biological treatment prior to apremilast, seven (17.0%) both before and after apremilast and 25 (61.0%) after apremilast. One patient received concomitant treatment with adalimumab and apremilast. Most patients (85.4%) received apremilast as treatment for psoriasis. Reasons for starting apremilast were lack of efficacy with previous treatments (85.4%) and adverse effects or contraindication to previous treatments (14.6%), without statistically significant differences between patients who had received a previous biologic and those who had not. Drug survival was not influenced by previous biological treatment, but we found an increased risk of drug discontinuation in patients with chronic kidney disease (log-rank p = 0.028). The main reason of apremilast withdrawal was lack of adequate disease control (60.0%), most of whom required treatment with biologics. Therefore, despite the extensive development of new therapies for psoriasis and other dermatological conditions, apremilast is a widely used drug even in patients who are candidates for biologic treatment. Its initiation is more frequent due to poor disease control than because of other therapies contraindications.

Phytochemical Composition of Lichen Parmotrema hypoleucinum (J. Steiner) Hale from Algeria.

In this work, we carried out studies of the chemical composition of hexane, chloroform and ethanol extracts from two samples of the lichen Parmotrema hypoleucinum collected in Algeria. Each sample of the lichen P. hypoleucinum was collected on two different supports: Olea europaea and Quercus coccifera. Hexane extracts were prepared, in Soxhlet; each hexane extract was fractionated by its solubility in methanol; the products soluble in methanol were separated (cold): 1-Hexane, 2-Hexane; and the products insoluble in methanol (cold): 1-Cires, 2-Cires. A diazomethane esterified sample of 1-Hexane, 2-Hexane, 1-Cires and 2-Cires was analyzed by GC-MS, and the components were identified as methyl esters. In the 1-Hexane and 2-Hexane fractions, the methyl esters of the predominant fatty acids in the lichen were identified: palmitic acid, linoleic acid, oleic acid and stearic acid; a hydrocarbon was also identified: 13-methyl-17-norkaur-15-ene and several derivatives of orsellinic acid. In the 1-Cires and 2-Cires fractions, the previous fatty acids were no longer observed, and only the derivatives of orsellinic acid were found. The analysis of the 1-Hexane, 2-Hexane fractions by HPLC-MS/MS allows us to identify different chemical components, and the most characteristic products of the lichen were identified, such as Atranol, Chloroatranol, Atranorin and Chloroatranorin. In the fractions of 1-Cires and 2-Cires, the HPLC-MS/MS analysis reveals that they are very similar in their chemical components; the characteristic products of this lichen in this fraction are Atranorin and Chloroatranorin. In the extracts of chloroform, 1-Chloroform and 2-Chloroform, the analysis carried out by HPLC-MS/MS shows small differences in their chemical composition at the level of secondary products; among the products to be highlighted for this work, we have chloroatranorin, the stictic acid, norstictic acid and other derivatives. In the analysis of the most polar extracts carried out in ethanol: 1-Ethanol and 2-Ethanol, HPLC-MS/MS analysis shows very similar chemical compositions in these two extracts with small differences. In these extracts, the following acids were identified as characteristic compounds of this lichen: constictic acid, stictic acid, substictic acid and methylstictic acid. In the HPLC-MS/MS analysis of all these extracts, alectoronic acid was not found.

Synthesis and Modeling of Ezetimibe Analogues.

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl ß-lactam is described starting from Baylis-Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.

1,3-Cyclohexadien-1-Als: Synthesis, Reactivity and Bioactivities.

In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels-Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics-it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.

Multicomponent Domino Reaction in the Asymmetric Synthesis of Cyclopentan[c]pyran Core of Iridoid Natural Products.

The asymmetric synthesis of a compound with the cyclopentan[c]pyran core of iridoid natural products in four steps and 40% overall yield is reported. Our methodology includes a one-pot tandem domino reaction which provides a trisubstituted cyclopentane with five new completely determined stereocenters, which were determined through 2D homo and heteronuclear NMR and n.O.e. experiments on different compounds specially designed for this purpose, such as a dioxane obtained from a diol. Due to their pharmaceutical properties, including sedative, analgesic, anti-inflammatory, CNS depressor or anti-conceptive effects, this methodology to produce the abovementioned iridoid derivatives, is an interesting strategy in terms of new drug discovery as well as pharmaceutical development.

Antibacterial Natural Halimanes: Potential Source of Novel Antibiofilm Agents.

The development of new agents against bacteria is an urgent necessity for human beings. The structured colony of bacterial cells, called the biofilm, is used to defend themselves from biocide attacks. For this reason, it is necessary to know their structures, develop new agents to eliminate them and to develop new procedures that allow an early diagnosis, by using biomarkers. Among natural products, some derivatives of diterpenes with halimane skeleton show antibacterial activity. Some halimanes have been isolated from marine organisms, structurally related with halimanes isolated from Mycobacterium tuberculosis. These halimanes are being evaluated as virulence factors and as tuberculosis biomarkers, this disease being one of the major causes of mortality and morbidity. In this work, the antibacterial halimanes will be reviewed, with their structural characteristics, activities, sources and the synthesis known until now.

A Novel Cytotoxic Conjugate Derived from the Natural Product Podophyllotoxin as a Direct-Target Protein Dual Inhibitor.

Natural products are the ideal basis for the design of novel efficient molecular entities. Podophyllotoxin, a naturally occurring cyclolignan, is an example of natural product which displays a high versatility from a biological activity point of view. Based on its unique chemical structure, different derivatives have been synthesized presenting the original antitumoral properties associated with the compound, i.e., the tubulin polymerization inhibition and arising anti-topoisomerase II activity from structural modifications on the cyclolignan skeleton. In this report, we present a novel conjugate or hybrid which chemically combines both biological activities in one single molecule. Chemical design has been planned based in our lead compound, podophyllic aldehyde, as an inhibitor of tubulin polymerization, and in etoposide, an approved antitumoral drug targeting topoisomerase II. The cytotoxicity and selectivity of the novel synthetized hybrid has been evaluated in several cell lines of different solid tumors. In addition, these dual functional effects of the novel compound have been also evaluated by molecular docking approaches.

Reactive perforating collagenosis: a rare side effect associated with sorafenib.

We present the case of a patient with a debut of reactive perforating collagenosis associated with the use of Sorafenib for stage IV hepatocarcinoma, very successfully controlled with local corticotherapy and systemic antihistamines. This is an extremely rare side effect associated with this treatment, as only another eleven cases of acquired perforating dermatoses associated with Sorafenib or other multi-kinase inhibitors have been found in the medical literature. Given the unusual nature of this presentation, high clinical suspicion and a correct histopathological study are indispensable for its correct filiation and treatment.

The Methylene-Cycloalkylacetate (MCA) Scaffold in Terpenyl Compounds with Potential Pharmacological Activities.

Recently, the methylene-cycloakylacetate (MCA) scaffold has been reported as a potential pharmacophore for neurite outgrowth activity. In this work, natural diterpenes that embed MCA fragments are reviewed, as they are major components of Halimium viscosum: ent-halimic acid, the prototype for these bioactive compounds. Herein, structures, sources, and activities for the natural diterpenes, as well as their synthetic derivatives of interest, are reviewed.

Halimane diterpenoids: sources, structures, nomenclature and biological activities.

Covering: 1970 to 2017 Diterpenes with a halimane skeleton constitute a small group of natural products that can be biogenetically considered as being between labdane and clerodane diterpenoids. Some of these compounds show biological activities, such as antitumour, mosquito repellency, germination inhibition and antimicrobial, as well as being biomarkers for tuberculosis. To the best of our knowledge, there are no reviews on these compounds. In this review, halimane skeleton diterpenoids are classified according to their biogenetic origin, characterization and/or the enzymes involved in their biosynthesis. Herein, a review of their synthesis or synthetic approaches is communicated.

Acceptability and effectiveness of using mobile applications to promote HIV and other STI testing among men who have sex with men in Barcelona, Spain.

OBJECTIVE: To evaluate the acceptability and effectiveness of a pilot intervention programme using gay geosocial mobile applications (apps) to offer rapid HIV and other STI tests to men who have sex with men (MSM) in Barcelona between December 2015 and March 2016. METHODOLOGY: We offered rapid HIV, syphilis and hepatitis C testing by sending private messages on apps for sexual and social encounters. Acceptance was defined as the proportion of users who favourably responded to the message and effectiveness was defined as the proportion of users who attended our facilities among those who were interested in attending. To identify variables associated with the response to the messages, multivariate logistic regression was used. Adjusted OR (ORa) and 95% CIs were calculated. We collected information on sociodemographics, sexual behaviours and app usage from the contacted user profiles and from users who attended our facilities. A descriptive analysis was carried out. RESULTS: 2656 individual messages were sent. Overall, a 38.4% response rate was obtained, 83.0% of them found it acceptable to receive the unsolicited message, and 73.2% effectiveness was obtained. Responders had higher odds of being 45 years or older (ORa=1.48; 95% CI 1.06 to 2.08), being connected at the moment the message was sent or during the previous hour (ORa=1.92; 95% CI 1.38 to 2.68), having a profile photo not exposing bare chest or abdomen (ORa=1.44; 95% CI 1.07 to 1.92) and using the Grindr app (ORa=1.39; 95% CI 1.12 to 1.73). Of those who were tested and took the survey (n=77), 45.5% had not taken an HIV test in over a year, 24.7% had had a previous STI diagnosis, 51.4% had reported anal sex without condom and 52% had consumed alcohol or drugs for sex. CONCLUSIONS: The response rate, acceptance and effectiveness observed in this study indicate that this strategy could be a useful tool for promoting STI testing among high-risk MSM population.

Marine Alkylpurines: A Promising Group of Bioactive Marine Natural Products.

Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and biological properties are considered together with synthetic approaches towards the natural products and bioactive analogues. This review contributes to studies of structure-activity relationships for these metabolites and highlights the potential of the sea as a source of new lead compounds in diverse therapeutic fields.