Arlan da Silva Gonçalves

Context: Human kinesin Eg5 is essential for bipolar spindle assembly, and most allosteric inhibitors bind to the canonical pocket formed by the α2 helix, loop 5, and the α3 helix. Eleven thiazolo[3,2- a ]pyrimidinethiones were evaluated as ligands for two sites in Eg5: this canonical pocket and an alternative region near loop 8. All derivatives showed favorable docking poses at both sites, with average energies of -7.95 and -7.79 kcal.mol ⁻¹ for the loop 5 and loop 8 sites, respectively, whereas monastrol favored loop 5 by 1.6 kcal.mol ⁻¹ . Compounds 1a and 2d remained associated with both sites during 500 ns simulations, with ligand root-mean-square deviations between 1.00 and 1.53 Å. MM-PBSA estimates ranged from -26.02 to -22.92 kcal.mol ⁻¹ , compared with -22.14 kcal.mol ⁻¹ for monastrol. RMSF calculations revealed site- and ligand-dependent redistribution of mobility in loop 5, loop 8, Switch I, Switch II, the microtubule-binding site, the cover-neck bundle, and the neck linker. These results indicate that this scaffold is promising for the exploration of alternative allosteric sites in Eg5, although experimental confirmation is required. Method: The Switch II segment was reconstructed with SWISS-MODEL and evaluated with PDBsum. The structures were prepared with PDB2PQR, AutoDockTools, and Open Babel. Redocking compared AutoDock Vina, QuickVina 2, and QuickVina-W, and QuickVina-W with exhaustiveness 32 was selected. Six systems were simulated for 500 ns in GROMACS using the OPLS-AA/L force field, TIP3P water, and ligand parameters obtained with ACPYPE. Visual Molecular Dynamics was used for trajectory measurements, Discovery Studio Visualizer for interaction analysis, and g_mmpbsa for binding-energy estimation and per-residue decomposition.

Head and neck cancer (HNC) remains a major therapeutic challenge due to its biological heterogeneity and limited response to current treatments, highlighting the need for more effective and less toxic therapeutic strategies. Annona coriacea Mart., a plant native to the Brazilian Cerrado, is a source of bioactive acetogenins. In this study, we evaluated the antitumor effects of acetogenin-enriched fractions from A. coriacea using in vitro and in vivo models of HNC. The fractions exhibited cytotoxic activity against FaDu and HN13 cells, with IC50 values ranging from 2.42 to 8.25 μg/mL and from 1.61 to 12.57 μg/mL, respectively, while showing lower toxicity toward nontumor cells. Mechanistic analyses suggested the involvement of mitochondrial-associated apoptotic-like and necroptotic cell death processes. Molecular docking analyses indicated a possible modulatory interaction between acetogenins and tumor necrosis factor receptor 1 (TNFR1). In vivo, the selected fraction ACL3 reduced tumor growth and angiogenesis in the CAM model without inducing vascular irritation, as confirmed by the HET-CAM assay. Together, these findings demonstrate that A. coriacea acetogenin-rich fractions exhibit selective antitumor activity, induce mitochondrial-mediated and necroptosis-related cell death mechanisms, and inhibit tumor-associated angiogenesis, supporting their potential as promising candidates for further preclinical investigation in HNC.

This study focuses on presenting the effect of a magnetic field on paired graphene and cooper nanostructures (NS), with the objective of separating then.The graphene nanostructure (GNE) here selected is the coronene, shown before as a good nanographene model. Using the ORCA 5.0.4 software, computational calculations were performed to simulate the application of magnetic fields with intensities rising from 0 to 20 T at 300 K, with the RIJCOSX def2‐svp/C def2/J 6‐31G* basis set. The results show that increasing the magnetic field in the GNE/Cu coupled leads to a increase in the adsorption energy between the pair, which can provide the separation of the NS.

Phytopathogenic fungi like Fusarium graminearum are the cause of the disease gibberellosis, also known as Fusarium head blight (FHB). This disease shows significant losses in agriculture and effects on global economy. Nevertheless, this condition can be reduced with the use of commercial fungicides. Thus, this work describes computational studies performed on a group of natural products triazole derivatives using as starting point a small library of quinazolines synthesized by the literature. These quinazolines were applied to build QSAR models. Furthermore, using the Swiss Model server, a comparative modelling of the β-tubulin protein was realized to test the models and the compound 15, a triazole derivative of thymol successfully was further through both the QEPest and ProTox II toxicity tests. The behavior and stability between compound 15 and β-tubulin were then evaluated by 200 ns of molecular dynamics in comparison to carbendazim as standard inhibitor. Finally, the compound 15 revealed a stable complex with the protein throughout the simulation, exhibiting low fluctuations in the RMSF, indicating good interactions with the residues present. The investigation of the free energy of binding supports this, showing that whereas carbendazim had an MM/GBSA of -18 kcal/mol, thymol-derived 15 had an MM/GBSA of -44 kcal/mol.

Coffee is characterized by a complex chemical matrix that significantly influences its organoleptic properties and market value. This complexity is driven by factors such as botanical species, geographical origin, cultivation conditions, and post-harvest processing methods. Metabolomic studies aim to elucidate how these factors impact the biosynthesis of metabolites that contribute to the sensory qualities of high-quality coffee. Among various analytical techniques, liquid chromatography-mass spectrometry (LC-MS) is particularly effective for separating, identifying, and quantifying these compounds. Most metabolomic studies employ high-resolution mass spectrometry (HRMS) for its superior mass accuracy (n to comprehensively profile coffee metabolites, identifying 60 compounds, including polar compounds and their isomers such as chlorogenic acids, carbohydrates, amino acids, alkaloids, glycosylated diterpenes, and flavonoids. Fragmentation mechanisms were proposed and discussed. The results demonstrate the effectiveness of LC-ESI(±)LTQ MSⁿ in a detailed metabolomic analysis, providing a robust platform for future research in coffee metabolomics.

Context This study presents quantum chemical analysis of 14 distinct carbon-based nanostructures (CBN), ranging from simple molecules, like benzene, to more complex structures, such as coronene, which serves as an exemplary graphene-like model. The investigation focuses on elucidating the relationships between molecular orbital (MO) energies, the energy band gaps, electron occupation numbers (eON), electronic conduction, and the compound topologies, seeking to find the one that approaches most of a graphene-like structure for in silico studies. Through detailed examination of molecular properties including chemical hardness and chemical potential, we demonstrate that the electronic exchange between orbitals is directly influenced by the structural topology of the carbon-based nanostructures, as the electron occupation numbers and the molecular orbital energies. Raman theoretical analysis was performed, ensuring the approximation to a graphene structure by its experimental fingerprint comparison. The correlations presented here offer an approach for anticipating electronic conductivity in graphene-like materials, as well as the confirmation of coronene as a graphene nanostructure for theoretical analyses. Method The models were designed at Ghemical software optimized at Tripos5.2 force field and properly protonated on the peripheral carbons. The models were then optimized by PM7 semiempirical method using MOPAC2016 to minimize the gradient energy before applying the DFT calculations. After that, the model’s geometry was finally optimized at ab initio B3LYP hybrid functional and 6-31 G* basis, using ORCA5.0.4. The eON, the MO energies and the Raman spectrum were obtained with the same methods, making possible the spectrum extraction without the interference of H atoms, approaching the analyses to graphene-like topologies.

Phosphorus-containing graphene-based hybrids are materials with outstanding properties for diverse applications. In this work, an easy route to produce phosphorus-graphene oxide hybrid materials is described, involving the use of variable amounts of H₃PO₄ and H₂SO₄ during the reaction of oxidation of a graphitic precursor. The physical and chemical features of the hybrids change significantly with the variation in the acid amounts used in the syntheses. XPS and solid-state ¹³C and ³¹P NMR results show that the hybrids contain large amounts of oxygen functional groups, with the phosphorus incorporation proceeding mostly through the formation of phosphate-like linkages and other functions with C–O–P bonds. The experimental findings are supported by DFT calculations, which allow the assessment of the energetics and the geometry of the interaction between phosphate groups and graphene-based models; these calculations are also used to predict the chemical shifts in the ³¹P and ¹³C NMR spectra of the models, which show good agreement with the experimentally observed solid-state NMR spectra.

Human exposure to ultraviolet (UV) radiation leads photochemical excitation processes in the skin, causing problems to human health. The use of photoprotectors helps to minimize these intrinsic hazards. Benzophenone molecules stand out for the absorption of energy in the UVA and UVB range and structural changes in these, it is an area of ​​interest to obtain safer and more effective molecules. This work applied the full factorial design methodology 24 in an investigation by molecular modeling using semi-empirical method PM7, in order to evaluate the impact generated on the decrease of the energy GAP with the insertion of OH (level +) and H (level –-). The results showed unfavorable and favorable contributions between interactions and in the main effect, and the compounds disubstituted in ortho and para position for the same aromatic ring showed a better percentage of contribution, indicating that these conditions are relevant for greater reactivity compared to the others. Thus, we conclude that the use of the experimental planning methodology is an ally in obtaining information for planning new protective filtersmore stable and safe.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.