Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines-From the Synthesis to 3D-Cell Culture Effects.

Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness.

Insights into nucleoside hydrolase from Leishmania donovani inhibition: A new bioaffinity chromatography-based screening assay and docking studies.

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs).

Teaching in the Light of Activity Theory Applied to Preschool: Reflections on Brazilian Practice.

Background: Activity Theory applied by the teacher to preschool education favors the development of new psychological formations, such as perception, attention, memory, thought, language, and voluntary self-regulation, which prepare the child for school.

Objective: To highlight the contributions of N.F.

Nucleoside hydrolase immobilized on magnetic particles as a tool for onflow screening and characterization of inhibitors.

Nucleoside Hydrolases (NH) are considered a target for the development of new antiprotozoal agents. The development of new and automated screening assays for the identification of NH inhibitors can accelerate the first stages of the drug discovery process. In this work, NH from Leishmania donovani (LdNH) was covalently immobilized onto magnetic particles (LdNH-MPs) and trapped by magnets into a TFE tube to yield an immobilized enzyme reactor (IMER).

Ligand fishing as a tool to screen natural products with anticancer potential.

Cancer is the second leading cause of death in the world and its incidence is expected to increase with the aging of the world's population and globalization of risk factors. Natural products and their derivatives have provided a significant number of approved anticancer drugs and the development of robust and selective screening assays for the identification of lead anticancer natural products are essential in the challenge of developing personalized targeted therapies tailored to the genetic and molecular characteristics of tumors. To this end, a ligand fishing assay is a remarkable tool to rapidly and rigorously screen complex matrices, such as plant extracts, for the isolation and identification of specific ligands that bind to relevant pharmacological targets.

Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion.

Prion Diseases or Transmissible Spongiform Encephalopathies are neurodegenerative conditions associated with a long incubation period and progressive clinical evolution, leading to death. Their pathogenesis is characterized by conformational changes of the cellular prion protein-PrP-in its infectious isoform-PrP-which can form polymeric aggregates that precipitate in brain tissues. Currently, there are no effective treatments for these diseases.

Magnetic particles for enzyme immobilization: A versatile support for ligand screening.

Enzyme inhibitors represent a substantial fraction of all small molecules currently in clinical use. Therefore, the early stage of drug-discovery process and development efforts are focused on the identification of new enzyme inhibitors through screening assays. The use of immobilized enzymes on solid supports to probe ligand-enzyme interactions have been employed with success not only to identify and characterize but also to isolate new ligands from complex mixtures.

Discovery of a Novel Inhibitor of Human Purine Nucleoside Phosphorylase by a Simple Hydrophilic Interaction Liquid Chromatography Enzymatic Assay.

Human purine nucleoside phosphorylase (HsPNP) belongs to the purine salvage pathway of nucleic acids. Genetic deficiency of this enzyme triggers apoptosis of activated T-cells due to the accumulation of deoxyguanosine triphosphate (dGTP). Therefore, potential chemotherapeutic applications of human PNP inhibitors include the treatment of T-cell leukemia, autoimmune diseases and transplant tissue rejection.

Novel rivaroxaban-loaded poly(lactic-co-glycolic acid)/poloxamer nanoparticles: preparation, physicochemical characterization, in vitro evaluation of time-dependent anticoagulant activity and toxicological profile.

Rivaroxaban (RXB), an oral direct factor Xa inhibitor, presents innovative therapeutic profile. However, RXB has shown adverse effects, mainly due to pharmacokinetic limitations, highlighting the importance of developing more effective formulations. Therefore, this work aims at the preparation, physicochemical characterization and in vitro evaluation of time-dependent anticoagulant activity and toxicology profile of RXB-loaded poly(lactic-co-glycolic acid) (PLGA)/poloxamer nanoparticles (RXBNps).

Solid-Supported Proteins in the Liquid Chromatography Domain to Probe Ligand-Target Interactions.

Ligand-target interactions play a central role in drug discovery processes because these interactions are crucial in biological systems. Small molecules-proteins interactions can regulate and modulate protein function and activity through conformational changes. Therefore, bioanalytical tools to screen new ligands have focused mainly on probing ligand-target interactions.

Development of a Method for the Quantification of Clotrimazole and Itraconazole and Study of Their Stability in a New Microemulsion for the Treatment of Sporotrichosis.

Sporotrichosis occurs worldwide and is caused by the fungus . This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be effective against yeasts.

Cathepsin D immobilized capillary reactors for on-flow screening assays.

The treatment of diseases using enzymes as targets has called for the development of new and reliable methods for screening. The protease cathepsin D is one such target involved in several diseases such as tumors, degenerative processes, and vital processes of parasites causing schistosomiasis. Herein, we describe the preparation of a fused silica capillary, cathepsin D (CatD)-immobilized enzyme reactor (IMER) using in a multidimensional High Performance Liquid Chromatography-based method (2D-HPLC) and zonal affinity chromatography as an alternative in the search for new ligands.

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays.

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation, identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed.

Prion protein-coated magnetic beads: synthesis, characterization and development of a new ligands screening method.

Prion diseases are characterized by protein aggregation and neurodegeneration. Conversion of the native prion protein (PrP(C)) into the abnormal scrapie PrP isoform (PrP(Sc)), which undergoes aggregation and can eventually form amyloid fibrils, is a critical step leading to the characteristic path morphological hallmark of these diseases. However, the mechanism of conversion remains unclear.

Evaluation of capillary chromatographic supports for immobilized human purine nucleoside phosphorylase in frontal affinity chromatography studies.

The aim of this work was to optimize the preparation of a capillary human purine nucleoside phosphorylase (HsPNP) immobilized enzyme reactor (IMER) for characterization and affinity screening studies of new inhibitors by frontal affinity chromatography coupled to mass spectrometry (FAC-MS). For this purpose two monolithic supports, a Chromolith Speed Rod (0.1mm I.

Immobilized purine nucleoside phosphorylase from Schistosoma mansoni for specific inhibition studies.

The parasite Schistosoma mansoni (Sm) depends exclusively on the salvage pathway for its purine requirements. The enzyme purine nucleoside phosphorylase (PNP) is, therefore, a promising target for development of antischistosomal agents and an assay for screening of inhibitors. To enable this, immobilized SmPNP reactors were produced.

Acetylcholinesterase capillary enzyme reactor for screening and characterization of selective inhibitors.

The aim of the present work is to report on the optimized preparation of capillary enzyme reactors (ICERs) based on acetylcholinesterase (AChE, EC 3.1.1.

Capillary bioreactors based on human purine nucleoside phosphorylase: a new approach for ligands identification and characterization.

The enzyme purine nucleoside phosphorylase (PNP) is a target for the discovery of new lead compounds employed on the treatment severe T-cell mediated disorders. Within this context, the development of new, direct, and reliable methods for ligands screening is an important task. This paper describes the preparation of fused silica capillaries human PNP (HsPNP) immobilized enzyme reactor (IMER).

Restricted-access media supports for direct high-throughput analysis of biological fluid samples: review of recent applications.

This review presents an update on the use of restricted-access materials (RAMs) for direct injection of biological samples. The fundamental improvements in the preparation of tailored RAMs and the diversity of applications with these phases are presented. Insights into diminishing the matrix effect by the use of RAM supports in methods by LC-MS and into the low number of methods for enantiomeric separations by direct injections of biological samples are addressed.

The development of an immobilized enzyme reactor containing glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi: the effect of species' specific differences on the immobilization.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in the life cycle of the Trypanosoma cruzi, and an immobilized enzyme reactor (IMER) has been developed for use in the on-line screening for GAPDH inhibitors. An IMER containing human GAPDH has been previously reported; however, these conditions produced a T. cruzi GAPDH-IMER with poor activity and stability.