Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 5 Articles
Nanoparticles and nanosized materials offer huge potential in the field of drug delivery. One key aspect that dictates their successful development is the need to understand how they interact with cells at both the macro and molecular level. Delineating such interactions is vital if nanomaterials are to be targeted not only to particular organs and tissues, but also to individual cell types and ultimately specific subcellular locations. In this regard, the development of appropriate in vitro cell models is an essential prerequisite before animal and human trials. In recent years, as the methodology for their growth has been refined, there has been a huge expansion in the use of pre-clinical 3D cell culture models, particularly spheroids and organoids. These models are attractive because they can be combined with high-resolution fluorescence imaging to provide real-time information on how nanomaterials interact with cells. Confocal fluorescence microscopy and its associated modalities, along with highcontent screening and analysis, are powerful techniques that allow researchers the possibility of extracting spatial and temporal information at multiple levels from cells and entire 3D assemblies. In this review, we summarise the state of this field, paying particular emphasis to how imaging of such models is now beginning to provide rich quantitative data about nanomaterial entry and trafficking in cells growing in 3D. We also offer a perspective on the challenges faced by such approaches, and the important questions that the drug delivery field still needs to address....
G-protein-coupled receptors (GPCRs) are vital transmembrane proteins that regulate a wide range of physiological processes by transmitting extracellular signals into intracellular responses. Among them, the β2-adrenergic receptor (β2-AR) plays a central role in bronchodilation, smooth muscle relaxation, and cardiovascular modulation, making it a key therapeutic target for diseases such as asthma, chronic obstructive pulmonary disease (COPD), and hypertension. This study explores the potential of natural bioactive compounds like ephedrine, quercetin, catechin, and resveratrol as alternative ligands for β2-AR through molecular docking analysis. Using AutoDock 4.6, these compounds were docked with the binding site of the β2-AR (PDB ID: 2RH1), and their binding affinities and interaction map were evaluated. Results showed that all compounds exhibited favorable binding energies and stable interactions with key receptor residues, with quercetin demonstrating the highest affinity. The findings suggest that these natural compounds may serve as promising leads for the development of safer, plant-derived modulators of β2-AR, supporting the role of computational approaches in natural product-based drug discovery. However, as docking cannot determine functional activity, these findings should be interpreted as preliminary and require experimental validation....
Objectives: This study aims to investigate the impact of Gossypol on human cervical cancer cells and elucidate its mechanism of action to establish a foundation for further clinical investigations. Methods: Cell proliferation, migration, and invasion were evaluated through CCK-8, wound healing, and Transwell assays. Fe3O4-BP-Gossypol (Fe3O4@Gossypol) conjugates were synthesized by linking Fe3O4 with Gossypol using benzophenone crosslinking. Successful conjugation was confirmed through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible spectrophotometry (UV-Vis). Subsequent to co-incubation with HeLa cell lysates, Fe3O4@Gossypol complexes facilitated the magnetic enrichment and purification of target proteins, which were identified using high-resolution mass spectrometry (HR-MS). The identified targets underwent KEGG pathway and GO analyses, followed by molecular docking with Gossypol. HeLa cells were exposed to Gossypol at concentrations of 7.48, 14.96, and 29.92 μmol·L−1 for 48 h, and protein expression levels were quantified viaWestern blotting. Results: Gossypol notably suppressed cervical cancer cell proliferation, migration, and invasion. The integration of target fishing, network pharmacology, and molecular docking highlighted PIK3R2, MAPK1, and GRB2 as potential therapeutic targets. Western blot analysis revealed a dosedependent reduction in PIK3R2, GRB2, and MAPK1 expression in Gossypol-treated groups compared to controls (p < 0.05). Conclusions: Gossypol may exhibit anti-cervical cancer effects by modulating the PI3K/AKT signaling pathway....
The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25D3), regulates a number of physiological and pathological processes, including cell proliferation and differentiation. Thousands of analogues of 1,25D3 have been developed with the aim of selective effects for medical use. Here we describe the synthesis of two new unconventional vitamin D analogues bearing A-ring modifications with ortho-carborane (dicarba-o-closo-1,2- dodecaborane) units. The ligands function as agonists for VDR with similar antiproliferative activities as 1,25D3. Whereas mice treated with the analogues 4 and 5 exhibited similar hypercalcemic activities as 1,25D3, only compound 4 and 1,25D3 induced the strong activation of CYP24A1 mRNA expression but not compound 5....
Mycobacterium tuberculosis, the infectious agent behind tuberculosis (TB), underscores the significance of targeting enzymes such as arabinosyltransferases in drug development efforts. Benzothiozinone derivatives, which have been assessed for their effectiveness against TB, present a promising avenue for treatment. Utilizing a high virtual screening quantitative structure–activity relationship (QSAR-VS), a set of forty Benzothiozinone (C1–C40) compounds were investigated to build a robust model with satisfactory performance metrics (R2 = 0.82, R2 adj = 0.78, Ntest = 10, R2 test = 0.70). This model enabled the creation of databases containing new derivatives for screening drug-like properties and predicting MIC activity in TB treatment. The best-scoring compounds were screened by molecular docking with Mycobacterium tuberculosis kinases A and B (PDB code: 6B2P) and validated by molecular dynamics simulations to elucidate the most stable drug–protein interactions. Additionally, the MM-PBSA analysis shows that the strongest binding occurs in complexes X3, X4, and X6 with ΔGbind values of −8.2, −15.3, and −12.0 kcal/mol, respectively. Our in silico study aims to prospect these new anti-tubercular drugs and their potential development through perspective in vitro and in vivo assays....
Loading....