Insight into the epigenetic regulation of gene expression in the bloodstream and procyclic forms of through the involvement of G-quadruplexes.

This study explores how G-quadruplexes (G4s) influence gene expression during the transition between bloodstream (BF) and procyclic (PC) forms of . Computational analysis identified over 115 000 G4-prone sequences, with 63% predicted to form stable G4 structures. These sequences are enriched in regions associated with antigenic variation, suggesting a role in gene regulation.

-Dimethylaminonaphthyl-BODIPY Derivatives as Bioimaging Probes to Monitor Intracellular pH and Label Lysosomes and Lipid Droplets.

Fluorescence-based probes are a powerful tool for monitoring living systems in real time with spatiotemporal precision. 3-Difluoroborodipyrromethene (BODIPY) derivatives are widely used as bioimaging probes due to their excellent photophysical properties, high quantum yields, and chemical stability. In this context, we report two BODIPY-based fluorescent probes for visualizing lysosomes and lipid droplets as well as tracking intracellular pH variations within living cells.

Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential.

Background: Cell-free RNAs (cfRNAs) can be detected in biofluids and have emerged as valuable disease biomarkers. Accurate identification of the fragmented cfRNA signals, especially those originating from pathological cells, is crucial for understanding their biological functions and clinical value. However, many challenges still need to be addressed for their application, including developing specific analysis methods and translating cfRNA fragments with biological support into clinical applications.

DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease.

Bioimaging of Lysosomes with a BODIPY pH-Dependent Fluorescent Probe.

Fluorescence-based probes represent a powerful tool for noninvasive imaging of living systems in real time and with a high temporal and spatial resolution. Amongst several known fluorophores, 3-difluoroborodipyrromethene (BODIPY) derivatives have become a cornerstone for innovative fluorescent labelling applications, mainly due to their advantageous features including their facile synthesis, structural versatility and exceptional photophysical properties. In this context, we report a BODIPY-based fluorescent probe for imaging of lysosomes in living cells.

Chemically Tuning Resveratrol for the Effective Killing of Gram-Positive Pathogens.

In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics.

Magnetic Solid Nanoparticles and Their Counterparts: Recent Advances towards Cancer Theranostics.

Cancer is currently a leading cause of death worldwide. The World Health Organization estimates an increase of 60% in the global cancer incidence in the next two decades. The inefficiency of the currently available therapies has prompted an urgent effort to develop new strategies that enable early diagnosis and improve response to treatment.

Thiosugar naphthalene diimide conjugates: G-quadruplex ligands with antiparasitic and anticancer activity.

Glycosyl conjugation to drugs is a strategy being used to take advantage of glucose transporters (GLUT) overexpression in cancer cells in comparison with non-cancerous cells. Its extension to the conjugation of drugs to thiosugars tries to exploit their higher biostability when compared to O-glycosides. Here, we have synthesized a series of thiosugar naphthalene diimide conjugates as G-quadruplex ligands and have explored modifications of the amino sidechain comparing dimethyl amino and morpholino groups.

G-Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.

Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for regulating key biological activities and processes as transcription, replication, and repair in living cells. The information regarding their role and use as therapeutic drug targets in bacteria is still scarce. Here, we tested the biological activity of a G4-DNA ligand library, based on the naphthalene diimide (NDI) pharmacophore, against both Gram-positive and Gram-negative bacteria.

Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability.

Potential G-quadruplexes and i-Motifs in the SARS-CoV-2.

Quadruplex structures have been identified in a plethora of organisms where they play important functions in the regulation of molecular processes, and hence have been proposed as therapeutic targets for many diseases. In this paper we report the extensive bioinformatic analysis of the SARS-CoV-2 genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found.

Morphology and water flux of produced cellulose acetate membranes reinforced by the design of experiments (DOE).

Cellulose acetate (CA) ultrafiltration membranes were successfully prepared using the non-solvent induced phase separation (NIPS) methodology. This technique is used to produce porous membranes for a large variety of applications. However, the formation of a dense skin during the process reduces membrane pure water flux (PWF).

Symmetric and dissymmetric carbohydrate-phenyl ditriazole derivatives as DNA G-quadruplex ligands: Synthesis, biophysical studies and antiproliferative activity.

Here we present a novel G4-binding family of compounds based on a central core of phenyl ditriazole (PDTZ) modified with carbohydrates and phenyl pyrrolidinyl side-chains. Their synthesis was achieved using controlled click chemistry conditions to obtain both, symmetric and dissymmetric carb-PDTZ derivatives without any intermediate protecting steps through an optimized methodology. Binding of the new carb-PDTZ to a variety of G-quadruplex motifs was examined using different biophysical techniques.

G4-iM Grinder: when size and frequency matter. G-Quadruplex, i-Motif and higher order structure search and analysis tool.

We present G4-iM Grinder, a system for the localization, characterization and selection of potential G4s, i-Motifs and higher order structures. A robust and highly adaptable search engine identifies all structures that fit the user's quadruplex definitions. Their biological relevance, formation probability and presence of known-to-form structures are then used as filters.

A nanodelivered Vorinostat derivative is a promising oral compound for the treatment of visceral leishmaniasis.

There is currently no satisfactory treatment for visceral leishmaniasis; the disease is thus in desperate need of novel drugs. The ideal candidate should be effective, safe, affordable, and administered via the oral route. Histone deacetylases (HDACs) are involved in silencing critical regulatory pathways, including pro-apoptotic programs, and represent potential therapeutic targets for pharmacological interventions.

Enzymatic Synthesis of a Novel Pterostilbene α-Glucoside by the Combination of Cyclodextrin Glucanotransferase and Amyloglucosidase.

The synthesis of a novel α-glucosylated derivative of pterostilbene was performed by a transglycosylation reaction using starch as glucosyl donor, catalyzed by cyclodextrin glucanotransferase (CGTase) from sp. The reaction was carried out in a buffer containing 20% (/) DMSO to enhance the solubility of pterostilbene. Due to the formation of several polyglucosylated products with CGTase, the yield of monoglucoside was increased by the treatment with a recombinant amyloglucosidase (STA1) from var.

Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases.

Resveratrol is a naturally occurring stilbene which has shown promising results as treatment for several neurodegenerative diseases. However, its application is limited due to its low efficacy and bioavailability. Here, we have designed and synthesized alkylated resveratrol prodrugs combining structural modification to improve antioxidant and anti-inflammatory properties and the preparation of prodrugs to extend drug bioavailability.

G-Quadruplex Identification in the Genome of Protozoan Parasites Points to Naphthalene Diimide Ligands as New Antiparasitic Agents.

G-quadruplexes (G4) are DNA secondary structures that take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria, and viruses. Here, we present PQS searches on the genomes of T.

Enzymatic Synthesis of a Novel Neuroprotective Hydroxytyrosyl Glycoside.

The eco-friendly synthesis of non-natural glycosides from different phenolic antioxidants was carried out using a fungal β-xylosidase to evaluate changes in their bioactivities. Xylosides from hydroquinone and catechol were successfully formed, although the best results were obtained for hydroxytyrosol, the main antioxidant from olive oil. The formation of the new products was followed by thin-layer chromatography, liquid chromatography, and mass spectrometry.

Synthesis, Binding Properties, and Differences in Cell Uptake of G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates.

The G-quadruplexes (G4s) are currently being explored as therapeutic targets in cancer and other pathologies. Six carbohydrate naphthalene diimide conjugates (carb-NDIs) have been synthesized as G4 ligands to investigate their potential selectivity in G4 binding and cell penetration. Carb-NDIs have shown certain selectivity for G4 structures against DNA duplexes, but different sugar moieties do not induce a preference for a specific G4 topology.

Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents.

Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites.