Exploring marine toxins: comparative analysis of chemical reactivity properties and potential for drug discovery

Marine toxins, produced by various marine microorganisms, pose significant risks to both marine ecosystems and human health. Understanding their diverse structures and properties is crucial for effective mitigation and exploration of their potential as therapeutic agents. This study presents a comparative analysis of two hydrophilic and two lipophilic marine toxins, examining their reactivity properties and bioavailability scores. By investigating similarities among these structurally diverse toxins, valuable insights into their potential as precursors for novel drug development can be gained. The exploration of lipophilic and hydrophilic properties in drug design is essential due to their distinct implications on drug distribution, elimination, and target interaction. By elucidating shared molecular properties among toxins, this research aims to identify patterns and trends that may guide future drug discovery efforts and contribute to the field of molecular toxinology. The findings from this study have the potential to expand knowledge on toxins, facilitate a deeper understanding of their bioactivities, and unlock new therapeutic possibilities to address unmet biomedical needs. The results showcased similarities among the studied systems, while also highlighting the exceptional attributes of Domoic Acid (DA) in terms of its interaction capabilities and stability

Talarolide A and Talaropeptides A–D: Potential Marine-Derived Therapeutic Peptides with Interesting Chemistry and Biological Activity Studied through Density Functional Theory (DFT) and Conceptual DFT

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A–D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A–D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The molecular geometry optimizations and frequency calculations were conducted using the Density Functional Tight Binding (DFTBA) method. This was followed by a subsequent round of geometry optimization, frequency analysis, and computation of electronic properties and chemical reactivity descriptors. We employed the MN12SX/Def2TZVP/H2O model chemistry, utilizing the Gaussian 16 program and the SMD solvation model. The analysis of the global reactivity descriptors arising from CDFT was achieved as well as the graphical comparison of the dual descriptor DD revealing the areas of the molecules with more propensity to suffer a nucleophilic or electrophilic attack. Additionally, Molinspiration and SwissTargetPrediction were considered for the calculation of molecular characteristics and predicted biological targets. These include enzymes, nuclear receptors, kinase inhibitors, GPCR ligands, and ion channel modulators. The graphical results show that Talarolide A and the Talaropeptides A–D are likely to behave as protease inhibitors

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process.

To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies