Light-Driven Two-Step Preparation of 4-Chromanone Fused to Estrone Derivatives.

A protocol involving the irradiation of some 3-(2-alkenyl)estrone and 3-(2-alkenyl)-17-norestrone derivatives under a nitrogen atmosphere in organic solvents (both hexane and MeOH) followed by base-mediated intramolecular oxa-Michael cyclization reaction was investigated under steady-state conditions. The solvent effect and nature of the acyl group on the preparative photoreaction were studied and the multiplicity of the excited state was also demonstrated. The ortho-regioisomers were obtained in modest to good yields. Intramolecular based-mediate cyclization reaction of these synthons led to the formation of a set of novel substituted 4-chromanone moieties fused to estrone (and 17-norestrone) in good yields. This two-step sequential procedure involving a photochemical/intramolecular thermal cyclization strategy will be useful for the preparation of wide heterocyclic-fused-steroid compounds.

Toxicity evaluation of Pinus radiata D.Don bark wax for potential cosmetic application.

Radiata pine bark is a widely available organic waste, requiring alternative uses due to its environmental impact on soil, fauna, and forest fires. Pine bark waxes could be used as cosmetic substitutes, but their toxicity requires evaluation since pine bark may contain toxic substances or xenobiotics, depending on the extraction process. This study evaluates the toxicity of radiata pine bark waxes obtained through various extraction methods on human skin cells grown in vitro. The assessment includes using XTT to evaluate mitochondrial activity, violet crystal dye to assess cell membrane integrity, and ApoTox-Glo triple assay to measure cytotoxicity, viability, and apoptosis signals. Pine bark waxes extracted via T3 (acid hydrolysis and petroleum ether incubation) and T9 (saturated steam cycle, alkaline hydrolysis, and petroleum ether incubation) exhibit non-toxicity up to 2% concentration, making them a potential substitute for petroleum-based cosmetic materials. Integrating the forestry and cosmetic industries through pine bark wax production under circular economy principles could promote development while replacing petroleum-based materials. Extraction methodology affects pine bark wax toxicity in human skin cells due to the retention of xenobiotic compounds including methyl 4-ketohex-5-enoate; 1-naphthalenol; dioctyl adipate; eicosanebioic acid dimethyl ester; among others. Future research will investigate whether the extraction methodology alters the molecular structure of the bark, affecting the release of toxic compounds in the wax mixture.

Alkylation converts riboflavin into an efficient photosensitizer of phospholipid membranes.

A new decyl chain [-(CH2)9CH3] riboflavin conjugate has been synthesized and investigated. A nucleophilic substitution (SN2) reaction was used for coupling the alkyl chain to riboflavin (Rf), a model natural photosensitizer. As expected, the alkylated compound (decyl-Rf) is significantly more lipophilic than its precursor and efficiently intercalates within phospholipid bilayers, increasing its fluorescence quantum yield. The oxidative damage to lipid membranes photoinduced by decyl-Rf was investigated in large and giant unilamellar vesicles (LUVs and GUVs, respectively) composed of different phospholipids. Using a fluorogenic probe, fast radical formation and singlet oxygen generation was demonstrated upon UVA irradiation in vesicles containing decyl-Rf. Photosensitized formation of conjugated dienes and hydroperoxides, and membrane leakage in LUVs rich in poly-unsaturated fatty acids were also investigated. The overall assessment of the results shows that decyl-Rf is a significantly more efficient photosensitizer of lipids than its unsubstituted precursor and that the association to lipid membranes is key to trigger phospholipid oxidation. Alkylation of hydrophilic photosensitizers as a simple and general synthetic tool to obtain efficient photosensitizers of biomembranes, with potential applications, is discussed.

Impact of mobility restrictions on NO2 concentrations in key Latin American cities during the first wave of the COVID-19 pandemic.

Between March and June 2020, activity in the major cities of Latin America declined due to containment efforts implemented by local governments to avoid the rapid spread of COVID-19. Our study compared 2020 with the previous year and demonstrated a considerable drop in tropospheric NO2 levels obtained by the SENTINEL 5P satellite in major Latin American cities. Lima (47.5%), Santiago (36.1%), São Paulo (27%), Rio de Janeiro (23%), Quito (18.6%), Bogota (17.5%), Buenos Aires (16.6%), Guayaquil (15.3%), Medellin (14.2%), La Paz (9.5%), Belo Horizonte (7.8%), Mexico (7.6%) and Brasilia (5.9%) registered statistically significant decreases in NO2 concentrations during the study period. In addition, we analyzed mobility data from Google and Apple reports as well as meteorological information from atmospheric reanalysis data along with satellite fields between 2011 and 2020, and performed a refined multivariate analysis (non-negative matrix approximation) to show that this decrease was associated with a reduction in population mobility rather than meteorological factors. Our findings corroborate the argument that confinement scenarios may indicate how air pollutant concentrations can be effectively reduced and managed.

Synthesis, Characterization and Photocleavage of Bis-decyl Pteroic Acid: A Folate Derivative with Affinity to Biomembranes†.

Here, we provide mechanistic insight to the photocleavage of a compound in the folate family, namely pteroic acid. A bis-decyl chain derivative of pteroic acid was synthesized, structurally characterized and photochemically investigated. We showed that, like folic acid, pteroic acid and the decylated derivative undergo a photocleavage reaction in the presence of H2 O, while no reaction was observed in methanol solution. Furthermore, density functional theory calculations were carried out to predict relative stabilities of hypothetical mono-, bis- and tris-decylated pteroic acid derivatives to help rationalize the regioselectivity of the bis-decyl pteroic acid product. Additionally, the lipophilicity of the bis-decyl pteroic acid appears to confer a hydrophobic property enabling an interaction with biomembranes.

Detección y cuantificación de SARS-CoV-2 en plantas de tratamiento de aguas residuales de diferentes ciudades de Chile: hacia la implementación de una vigilancia centinela permanente / Detection and quantification of SARS-CoV-2 wastewater treatment plants from different cities in Chile; towards to a permanent sentinel surveillance

INTRODUCCIÓN: La cuantificación de SARS-CoV-2 en aguas residuales es una herramienta que permite determinar la tendencia de la circulación viral en un área geográfica determinada. OBJETIVO: Cuantificar el virus SARS-CoV-2 en 15 plantas de tratamiento de aguas residuales en diferentes ciudades de Chile para establecer una comparación con las variables de: i) casos activos por cada 100.000 habs.; ii) positividad diaria (casos nuevos); y iii) fases del plan de confinamiento. METODOLOGÍA: SARS-CoV-2 se concentró a partir de muestras de aguas residuales. Para obtener el número de genomas del virus por litro se realizó una cuantificación absoluta utilizando qRT-PCR. RESULTADOS: Entre enero y junio de 2021 se procesaron 253 muestras, siendo todas positivas para la presencia del virus. Asimismo, se logró determinar que la tasa de casos activos por cada 100.000 habs. es la variable que mejor se ajusta a las tendencias obtenidas con la cuantificación de la carga viral en las aguas residuales. CONCLUSIONES: La cuantificación de SARS-CoV-2 en las aguas residuales de manera permanente es una herramienta eficiente para determinar la tendencia del virus en un área geográfica determinada y, en conjunto con una vigilancia genómica, puede constituirse en una vigilancia centinela ideal generando alertas sobre futuros brotes.

BACKGROUND: The quantification of SARS-CoV-2 in wastewater is a tool that allows determining the trend of viral circulation in a particular geographical area. AIM: To quantify the SARS-CoV-2 virus in 15 wastewater treatment plants in different Chilean cities to establish a comparison with the variables of: i) Active cases per 100,000 inhabitants; ii) daily positivity (novel cases); and iii) phases of the lockdown strategy. METHODS: SARS-CoV-2 was concentrated from wastewater samples. To obtain the number of virus genomes per liter, absolute quantification was performed using qRT-PCR. RESULTS: Between January and June 2021, 253 samples were processed, all of which were positive for the presence of the virus. Likewise, it will be determined that the rate of active cases per 100,000 inhabitants is the variable that best fits the trends obtained with the quantification of the viral load in wastewater. CONCLUSIONS: The quantification of SARS-CoV-2 in wastewater as a continuous strategy is an efficient tool to determine the trend of the viral circulation in a delimited geographical area and, combined with genomic surveillance, it can constitute an ideal sentinel surveillance alert on future outbreaks.

The Sall2 transcription factor promotes cell migration regulating focal adhesion turnover and integrin ß1 expression.

SALL2/Sall2 is a transcription factor associated with development, neuronal differentiation, and cancer. Interestingly, SALL2/Sall2 deficiency leads to failure of the optic fissure closure and neurite outgrowth, suggesting a positive role for SALL2/Sall2 in cell migration. However, in some cancer cells, SALL2 deficiency is associated with increased cell migration. To further investigate the role of Sall2 in the cell migration process, we used immortalized Sall2 knockout (Sall2 -/- ) and Sall2 wild-type (Sall2 +/+ ) mouse embryonic fibroblasts (iMEFs). Our results indicated that Sall2 positively regulates cell migration, promoting cell detachment and focal adhesions turnover. Sall2 deficiency decreased cell motility and altered focal adhesion dynamics. Accordingly, restoring Sall2 expression in the Sall2 -/- iMEFs by using a doxycycline-inducible Tet-On system recovered cell migratory capabilities and focal adhesion dynamics. In addition, Sall2 promoted the autophosphorylation of Focal Adhesion Kinase (FAK) at Y397 and increased integrin ß1 mRNA and its protein expression at the cell surface. We demonstrated that SALL2 increases ITGB1 promoter activity and binds to conserved SALL2-binding sites at the proximal region of the ITGB1 promoter, validated by ChIP experiments. Furthermore, the overexpression of integrin ß1 or its blockade generates a cell migration phenotype similar to that of Sall2 +/+ or Sall2 -/- cells, respectively. Altogether, our data showed that Sall2 promotes cell migration by modulating focal adhesion dynamics, and this phenotype is associated with SALL2/Sall2-transcriptional regulation of integrin ß1 expression and FAK autophosphorylation. Since deregulation of cell migration promotes congenital abnormalities, tumor formation, and spread to other tissues, our findings suggest that the SALL2/Sall2-integrin ß1 axis could be relevant for those processes.

Enhancing the Thermal Conductivity of Amorphous Carbon with Nanowires and Nanotubes.

The thermal conductivity of nanostructures can be obtained using atomistic classical Molecular Dynamics (MD) simulations, particularly for semiconductors where there is no significant contribution from electrons to thermal conduction. In this work, we obtain and analyze the thermal conductivity of amorphous carbon (aC) nanowires (NW) with a 2 nm radius and aC nanotubes (NT) with 0.5, 1 and 1.3 nm internal radii and a 2 nm external radius. The behavior of thermal conductivity with internal radii, temperature and density (related to different levels of sp3 hybridization), is compared with experimental results from the literature. Reasonable agreement is found between our modeling results and the experiments for aC films. In addition, in our simulations, the bulk conductivity is lower than the NW conductivity, which in turn is lower than the NT conductivity. NTs thermal conductivity can be tailored as a function of the wall thickness, which surprisingly increases when the wall thickness decreases. While the vibrational density of states (VDOS) is similar for bulk, NW and NT, the elastic modulus is sensitive to the geometrical parameters, which can explain the enhanced thermal conductivity observed for the simulated nanostructures.

Terrestrial Ant Assemblages (Hymenoptera: Formicidae) in Protected Forests and Grasslands in Three Ecoregions of Corrientes Province, Argentina.

A comparative study on forests and grasslands in three ecoregions (Humid Chaco, Espinal, and Paranaense) was conducted in two protected areas in northeastern Argentina: Iberá National Park and Mburucuyá National Park. The effects of habitat heterogeneity (vegetation cover) on terrestrial ant (Formicidae) assemblages were analyzed and compared. The habitat heterogeneity hypothesis-which predicts that when environmental structural complexity increases, the species richness will also increase-was tested. Two sites were selected in each ecoregion. A forest and a grassland were surveyed in each site, using unbaited pitfall traps from October 2013 to February 2014. Overall, 5,465 ants belonging to 37 species were collected, 32 of which were present in forests and 26 in grasslands. Solenopsis invicta Buren (Hymenoptera: Formicidae) and Pheidole radoszkowskii Mayr (Hymenoptera: Formicidae) were the most abundant species. Formicidae assemblages were compared in terms of abundance, species richness, and diversity between habitats and ecoregions. The results of this study support the habitat heterogeneity hypothesis, since we found a higher diversity of ants in more structured habitats (i.e., forest) in the three ecoregions analyzed. Also, the ant assemblages differed both between habitats and between ecoregions. Our findings provide the first assessment of terrestrial ant assemblages in natural habitats of the three ecoregions in Corrientes Province, Argentina.

Photochemistry of para substituted benzanilides in solution: Preparative and mechanistic studies.

Preparative and mechanistic studies on the photochemical reaction of a series of p-substituted benzanilides in polar and nonpolar solvents have been carried out. The aim of this work is mainly focused to show whether the reaction solvent and the electronic effects of the substituents affect the product distribution, the chemical yields and the rate of formation of the 5-substituted-2-aminobenzophenone derivatives. Application of the Hammett linear free energy relationship (LFER) on the rate of formation of 2-aminobenzophenone derivatives, on the lower energy band of the UV-visible absorption spectra of the benzanilides and 5-substituted-2-aminobenzophenone derivatives allows a satisfactory quantification of the substituent effects. Furthermore, the solvent effect was also analyzed on the photoreaction by means of the Reichardt's solvent parameter (ET(30). Finally, (TD-) DFT calculations have been carried out to support the trends observed experimentally.

Pseudorotaxane formation affected by stereo-electronic effects. A theoretical and experimental study.

We report a theoretical and experimental study on different complexes of pseudorotaxanes possessing pyridine axles. In order to evaluate the stereo-electronic effects of the methyl substituents in the pyridine ring, complexes with different substitution patterns were synthesized. In this way, it was possible to analyze the different behaviors of these complexes according to the positions of their methyl substituents. Combined techniques of molecular dynamics and quantum mechanical calculations with the help of molecular electrostatic potentials for a simpler visualization of the electronic effects were employed. We have sought experimental support of NMR spectroscopy analysis to corroborate the conclusions obtained from the molecular simulations. Our results not only clearly demonstrate that both electronic and steric effects play key roles in the feasibility of the formation of such complexes, but also the simulations reported here might predict the degree of difficulty of their formation. The combination of computational techniques employed here seems to be an excellent approach to be able to predict whether or not a complex can be formed and with what degree of difficulty. In addition, our experimental and theoretical results have allowed us to visualize the formation of external complexes in the rotaxanes reported here. In this case, the use of bolaforms with trimethylammonium groups at both ends was very useful to evaluate in detail the formation of the so-called external complexes in these systems.

Effect of Vegetation Types on Sarcophagidae (Diptera) in Ciervo de los Pantanos National Park, a Natural Remnant in a Highly Endangered Landscape.

Species diversity can be affected by the structure of vegetation, which may vary in height, density, and distribution of trees, shrubs, and other plant types, configuring different types of habitats. In this study, we evaluated the diversity of sarcosaprophagous Sarcophagidae communities inhabiting the remnant representative habitats protected in Ciervo de los Pantanos National Park: grasslands, forests, and wetlands. We hypothesized that the abundance and diversity of flesh flies would be higher in the grasslands and wetlands than in the forest patches. Samplings were carried out in each habitat type using baited traps during the four seasons in 2015, 2016, and 2019. We collected 585 sarcophagid flies of 17 species. Fifteen species were recorded in grasslands, twelve in the wetlands, and seven in the forests, Tricharaea (Sarcophagula) occidua (Fabricius) (Diptera: Sarcophagidae) being the most abundant (58.3% of the total sample). As expected, the highest abundance was recorded in grasslands whereas the lowest was found in forests. In addition, flesh fly abundance was affected by season. Sarcophagid assemblages differed between habitats and the overall dissimilarity was mainly explained by nestedness. This study provides important information about sarcosaprophagous sarcophagid flies in a little-studied protected natural area in Argentina, which is fundamental for their conservation and useful in forensic investigations.

Induced selectivity in the photochemistry of estrone derivatives in sustainable and micellar environment: preparative and mechanistic studies.

In this study, we carried out preparative and mechanistic studies on the photochemical reaction of a series of 3-acylestrone derivatives in confined and sustainable micellar environment under steady-state conditions and the results were compared with those obtained in cyclohexane solution. The aim of this work is mainly focused to show whether the nature of the surfactant (cationic, neutral and anionic) leads to noticeable selectivity in the photoproduct formation. The 3-acylestrone derivatives underwent the photo-Fries rearrangement, with concomitant homolytic fragmentation of the ester group and [1;3]-acyl migration. This pathway afforded the ortho-acyl estrone derivatives, the main photoproducts together with estrone. However, epimerization of the ortho regioisomer 2-acetylestrone and estrone through Norrish Type I photoreaction occurred involving the fragmentation of the C-α at the carbonyl group (C-17) of the steroid. UV-visible and 2D-NMR (NOESY) spectroscopies have been employed to measure the binding constant Kb and the location of the steroids within the hydrophobic core of the micelle.

The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes.

Diverse factors play roles in chromatin dynamics, including linker proteins. Among them are high mobility group (HMG) box family proteins and linker histones. In the yeast Saccharomyces cerevisiae, Hmo1 has been identified as an HMG-box protein. This protein displays properties that are in agreement with this allocation. However, a number of studies have postulated that Hmo1 functions as a linker histone in yeast. On the other hand, when discovered, the Hho1 protein was identified as a linker histone. While multiple studies support this classification, some findings point to characteristics of Hho1 that are dissimilar to those commonly assigned to linker histones. In order to better understand the roles played by Hmo1 and Hho1 in chromatin dynamics and transcriptional regulation, we performed several analyses directly comparing these two proteins. Our analyses of genome-wide binding profiles support the belonging of Hmo1 to the HMGB family and Hho1 to the linker histones family. Interestingly, by performing protein-protein interaction analyses we found that both Hmo1 and Hho1 display physical interaction with the ATP-dependent chromatin remodeling complexes RSC, ISW1a and SWI/SNF. Moreover, by carrying out nucleosome remodeling assays, we found that both proteins stimulate the activity of the ISW1a complex. However, in the case of RSC, Hmo1 and Hho1 displayed differential properties, with Hho1 mainly showing an inhibitory effect. Our results are in agreement with the opposite roles played by RSC and ISW1a in chromatin dynamics and transcriptional regulation, and expand the view for the roles played by Hho1 and linker histones.

Characterization of SALL2 Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks.

The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. Some studies support a tumor suppressor role and others an oncogenic role for SALL2, which seems to depend on the cancer type. An additional consideration is tissue-dependent expression of different SALL2 isoforms. Human and mouse SALL2 gene loci contain two promoters, each controlling the expression of a different protein isoform (E1 and E1A). Also, several improvements on the human genome assembly and gene annotation through next-generation sequencing technologies reveal correction and annotation of additional isoforms, obscuring dissection of SALL2 isoform-specific transcriptional targets and functions. We here integrated current data of normal/tumor gene expression databases along with ChIP-seq binding profiles to analyze SALL2 isoforms expression distribution and infer isoform-specific SALL2 targets. We found that the canonical SALL2 E1 isoform is one of the lowest expressed, while the E1A isoform is highly predominant across cell types. To dissect SALL2 isoform-specific targets, we analyzed publicly available ChIP-seq data from Glioblastoma tumor-propagating cells and in-house ChIP-seq datasets performed in SALL2 wild-type and E1A isoform knockout HEK293 cells. Another available ChIP-seq data in HEK293 cells (ENCODE Consortium Phase III) overexpressing a non-canonical SALL2 isoform (short_E1A) was also analyzed. Regardless of cell type, our analysis indicates that the SALL2 long E1 and E1A isoforms, but not short_E1A, are mostly contributing to transcriptional control, and reveals a highly conserved network of brain-specific transcription factors (i.e., SALL3, POU3F2, and NPAS3). Our data integration identified a conserved molecular network in which SALL2 regulates genes associated with neural function, cell differentiation, development, and cell adhesion between others. Also, we identified PODXL as a gene that is likely regulated by SALL2 across tissues. Our study encourages the validation of publicly available ChIP-seq datasets to assess a specific gene/isoform's transcriptional targets. The knowledge of SALL2 isoforms expression and function in different tissue contexts is relevant to understanding its role in disease.

H3K9 Methyltransferases Suv39h1 and Suv39h2 Control the Differentiation of Neural Progenitor Cells in the Adult Hippocampus.

In the dentate gyrus of the adult hippocampus new neurons are generated from neural precursor cells through different stages including proliferation and differentiation of neural progenitor cells and maturation of newborn neurons. These stages are controlled by the expression of specific transcription factors and epigenetic mechanisms, which together orchestrate the progression of the neurogenic process. However, little is known about the involvement of histone posttranslational modifications, a crucial epigenetic mechanism in embryonic neurogenesis that regulates fate commitment and neuronal differentiation. During embryonic development, the repressive modification trimethylation of histone H3 on lysine 9 (H3K9me3) contributes to the cellular identity of different cell-types. However, the role of this modification and its H3K9 methyltransferases has not been elucidated in adult hippocampal neurogenesis. We determined that during the stages of neurogenesis in the adult mouse dentate gyrus and in cultured adult hippocampal progenitors (AHPs), there was a dynamic change in the expression and distribution of H3K9me3, being enriched at early stages of the neurogenic process. A similar pattern was observed in the hippocampus for the dimethylation of histone H3 on lysine 9 (H3K9me2), another repressive modification. Among H3K9 methyltransferases, the enzymes Suv39h1 and Suv39h2 exhibited high levels of expression at early stages of neurogenesis and their expression decreased upon differentiation. Pharmacological inhibition of these enzymes by chaetocin in AHPs reduced H3K9me3 and concomitantly decreased neuronal differentiation while increasing proliferation. Moreover, Suv39h1 and Suv39h2 knockdown in newborn cells of the adult mouse dentate gyrus by retrovirus-mediated RNA interference impaired neuronal differentiation of progenitor cells. Our results indicate that H3K9me3 and H3K9 methyltransferases Suv39h1 and Suv39h2 are critically involved in the regulation of adult hippocampal neurogenesis by controlling the differentiation of neural progenitor cells.

Photochemical Behavior of Some Estrone Aryl and Methyl Sulfonates in Solution: Preparative and Mechanistic Studies.

Direct irradiation of estrone aryl and methyl sulfonates in different organic solvents under nitrogen atmosphere was investigated under steady-state conditions. The estrone derivatives reacted efficiently through the photo-Fries rearrangement reaction involving [1;3]-sulfonyl migration providing the ortho-sulfonyl estrone derivatives and estrone as the photoproducts. In addition, estrone and 2-arylsulfonyl estrone derivatives were epimerized involving a Norrish Type-I reaction. Chemical quenching and photosensitization experiments on the photoreaction have been also carried out to establish the photoreactive excited state. Likewise, the solvent effect and the nature of the sulfonyl group on the photoreactions have been also studied.

Seasonal Fluctuations in Sarcophagidae (Diptera: Calyptratae) Assemblages in the Humid Chaco Ecoregion, Argentina.

The seasonal fluctuations of flesh fly (Diptera: Sarcophagidae) assemblages were investigated from March 2015 to February 2016 in five habitat types in the Humid Chaco ecoregion, Chaco Province, Argentina. Three of the habitats were anthropized: an urban area, a cattle farm, and an alfalfa crop; and two were natural: a savanna and a forest. Flesh flies were collected monthly at 25 sampling points, five per habitat. In total, 5,790 male specimens comprising 55 species distributed in 15 genera were collected. The assemblage composition of flesh flies in each habitat and season was analyzed in terms of abundance, species richness, and diversity. In addition, the correlation between these community parameters and climatic factors (precipitation 7 and 14 d before samplings, temperature, and relative humidity) were evaluated in each habitat. The highest abundance and species richness of Sarcophagidae were registered in May (autumn) and June (winter), respectively. The lowest diversity values were observed between August and September (end of winter and early spring) in all habitats. However, flesh flies were present and well represented (in terms of species richness) throughout the year in all habitat types. Fluctuations in the abundance of the most abundant species collected were analyzed. The climatic factors were correlated with diversity and species richness in the urban, cattle farm, and savanna habitats. This study revealed that flesh fly assemblages differed temporally between different types of habitats in accordance with climatic factors and microclimate conditions.

Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies.

Mono- and bis-decylated lumazines have been synthesized and characterized. Namely, mono-decyl chain [1-decylpteridine-2,4(1,3H)-dione] 6a and bis-decyl chain [1,3-didecylpteridine-2,4(1,3H)-dione] 7a conjugates were synthesized by nucleophilic substitution (SN 2) reactions of lumazine with 1-iododecane in N,N-dimethylformamide (DMF) solvent. Decyl chain coupling occurred at the N1 site and then the N3 site in a sequential manner, without DMF condensation. Molecular orbital (MO) calculations show a p-orbital at N1 but not N3 , which along with a nucleophilicity parameter (N) analysis predict alkylation at N1 in lumazine. Only after the alkylation at N1 in 6a, does a p-orbital on N3 emerge thereby reacting with a second equivalent of 1-iododecane to reach the dialkylated product 7a. Data from NMR (1 H, 13 C, HSQC, HMBC), HPLC, TLC, UV-vis, fluorescence and density functional theory (DFT) provide evidence for the existence of mono-decyl chain 6a and bis-decyl chain 7a. These results differ to pterin O-alkylations (kinetic control), where N-alkylation of lumazine is preferred and then to dialkylation (thermodynamic control), with an avoidance of DMF solvent condensation. These findings add to the list of alkylation strategies for increasing sensitizer lipophilicity for use in photodynamic therapy.

Actualización general de inmunoterapia en cáncer / Cancer immunotherapy: an update

Cancer is one of the leading causes of death worldwide. The success rate of conventional anticancer therapeutic approaches such as chemotherapy is limited by the non-specific toxicity and low specificity towards specific tumors, which are highly dependent on the mutational burden present on each patient. Similarly, targeted therapies have proven to induce resistance in numerous malignancies. Therefore, immunotherapy has emerged as a better approach to discriminate between "the own" and "the non-own", which occurs through two types of mechanisms, innate and acquired immunity. Acquired immunity is one of the targets for new immunotherapeutic treatments, unleashing the power of antigen-specific T cells as a potential therapeutic weapon for cancer treatment. Thus, immunotherapy modifies the own immune system to increase the recognition and elimination of cancer cells by identifying these cancer antigens. One of the advantages of immunotherapy, when compared to conventional anticancer approaches, is the generation of long-term immunity (immunological memory). Currently, there are different potential types of immunotherapy in cancer to promote the modulation of the immune response. Among them, the use of cytokines, vaccines, viruses, monoclonal antibodies, and the generation of adaptive immune response cells have achieved successful results in some types of cancer.