Discovery of novel drug-like antitubercular hits targeting the MEP pathway enzyme DXPS by strategic application of ligand-based virtual screening.

In the present manuscript, we describe how we successfully used ligand-based virtual screening (LBVS) to identify two small-molecule, drug-like hit classes with excellent ADMET profiles against the difficult to address microbial enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS). In the fight against antimicrobial resistance (AMR), it has become increasingly important to address novel targets such as DXPS, the first enzyme of the 2--methyl-d-erythritol-4-phosphate (MEP) pathway, which affords the universal isoprenoid precursors. This pathway is absent in humans but essential for pathogens such as , making it a rich source of drug targets for the development of novel anti-infectives.

Differential biochemical and behavioral responses induced by cocaine and benzoylecgonine exposure to the red swamp crayfish Procambarus clarkii.

Cocaine (COC) and its main metabolite, the benzoylecgonine (BE), are the main illicit drugs measured in aquatic system worldwide, with concentrations up to hundreds of ng/L. Although their current environmental concentrations are low these molecules can induce adverse effects at sub-individual level in non-target organisms. In contrast, the information at individual and behavioral level are still scant.

Stereoselective Biocatalyzed Reductions of Ginger Active Components Recovered from Industrial Wastes.

Ginger is among the most widespread and widely consumed traditional medicinal plants around the world. Its beneficial effects, which comprise e. g.

Chiral 2-phenyl-3-hydroxypropyl esters as PKC-alpha modulators: HPLC enantioseparation, NMR absolute configuration assignment, and molecular docking studies.

Protein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous cellular functions, making them extensively studied and highly attractive drug targets. In our previous work, we identified in racemate 1-2, based on the 2-benzyl-3-hydroxypropyl ester scaffold, two new potent and promising PKCα and PKCδ ligands, targeting the C1 domain of these two kinases. Herein, we report the resolution of the racemates by enantioselective semi-preparative HPLC.

Apoptosis-mediated anticancer activity in prostate cancer cells of a chestnut honey (Castanea sativa L.) quinoline-pyrrolidine gamma-lactam alkaloid.

Prostate cancer (PCa) is the most common malignancy in men and represents the second leading cause of cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived endogenous metabolite kynurenic acid (KYNA) and of the lactam form of 3-2'-pyrrilonidinyl-kynurenic acid (3-PKA-L), alkaloids usually present in combination in chestnut honey.

Bioactive Phenolic Compounds From Agri-Food Wastes: An Update on Green and Sustainable Extraction Methodologies.

Phenolic compounds are broadly represented in plant kingdom, and their occurrence in easily accessible low-cost sources like wastes from agri-food processing have led in the last decade to an increase of interest in their recovery and further exploitation. Indeed, most of these compounds are endowed with beneficial properties to human health (e.g.

Novel Compounds Targeting the RNA-Binding Protein HuR. Structure-Based Design, Synthesis, and Interaction Studies.

The key role of RNA-binding proteins (RBPs) in regulating post-transcriptional processes and their involvement in several pathologies (, cancer and neurodegeneration) have highlighted their potential as therapeutic targets. In this scenario, Embryonic Lethal Abnormal Vision (ELAV) or Hu proteins and their complexes with target mRNAs have been gaining growing attention. Compounds able to modulate the complex stability could constitute an innovative pharmacological strategy for the treatment of numerous diseases.

Compounds Interfering with Embryonic Lethal Abnormal Vision (ELAV) Protein-RNA Complexes: An Avenue for Discovering New Drugs.

RNA-binding proteins play a key role in post-transcriptional processes. Among these proteins, embryonic lethal abnormal vision (ELAV) proteins are among the best described. ELAV proteins predominantly act as positive regulators of gene expression, and their dysregulation is involved in several pathologies, such as cancer, inflammation, and neurodegenerative diseases.

PKC in Regenerative Therapy: New Insights for Old Targets.

Effective therapies for chronic or non-healing wounds are still lacking. These tissue insults often result in severe clinical complications (i.e.

The role of chirality in a set of key intermediates of pharmaceutical interest, 3-aryl-substituted-γ-butyrolactones, evidenced by chiral HPLC separation and by chiroptical spectroscopies.

The enantiomers of four chiral 3-aryl-substituted-γ-butyrolactones, key intermediates for the preparation of compounds of pharmaceutical interest, were successfully isolated by enantioselective chromatography, employing the Chiralpak AD-H chiral stationary phase. For all compounds the same elution order was observed, as monitored by a full set of chiroptical methods that we employed, namely ORD (optical rotatory dispersion), ECD (electronic circular dichroism, or CD in the UV range), and VCD (vibrational circular dichroism, or CD in the IR range). By density functional theory (DFT) calculations we were able to determine that the first eluted enantiomer has (S) absolute configuration in all four cases.

Enantiomeric 4-Acylamino-6-alkyloxy-2 Alkylthiopyrimidines As Potential A3 Adenosine Receptor Antagonists: HPLC Chiral Resolution and Absolute Configuration Assignment by a Full Set of Chiroptical Spectroscopy.

The chiral separation of enantiomeric couples of three potential A3 adenosine receptor antagonists: (R/S)-N-(6-(1-phenylethoxy)-2-(propylthio)pyrimidin-4-yl)acetamide (), (R/S)-N-(2-(1-phenylethylthio)-6-propoxypyrimidin-4-yl)acetamide (), and (R/S)-N-(2-(benzylthio)-6-sec-butoxypyrimidin-4-yl)acetamide () was achieved by high-performance liquid chromatography (HPLC). Three types of chiroptical spectroscopies, namely, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD), were applied to enantiomeric compounds. Through comparison with Density Functional Theory (DFT) calculations, encompassing extensive conformational analysis, full assignment of the absolute configuration (AC) for the three sets of compounds was obtained.