Letters in Drug Design & Discovery - Online First

Hepatocellular carcinoma is the cancer with the highest mortality rate worldwide. Currently, existing treatments are not very effective for this disease. Different science areas have focused on developing new therapies, including nanomedicine. In-vitro studies have reported the anticancer activity of silver nanoparticles, particularly those coated with polyvinylpyrrolidone (AgNPs-PVP).

Characterize the effect of AgNPs on the HepG2 by bioinformatics analysis.

From a list of proteins, we performed in-silico analysis to predict protein-protein interaction, hub gene, gene ontology, KEGG pathways, hub gene expression, protein expression, survival, cell infiltration immune, and molecular docking of AgNPs-PVP to target proteins. Cytoscape and UCSF Chimera software, DAVID, UALCAN, TISIDB, and HDOCK databases were included in the predictive analysis.

Gene ontology and KEGG pathways showed that AgNP exposure causes cellular organelles dysregulation and deregulation of protein production mechanisms.

Additionally, metabolic pathways were altered, including glycolysis, gluconeogenesis, and amino acid biosynthesis. Hub genes RPS15, RPLP0, EEF1B2, RPL12, and NACA showed differential expression for gene expression, protein, and survival analysis. Furthermore, RPS15 and RPL12 were positively correlated with CD8+ T cell infiltration, and RPLP0, EEF1B2, and NACA were negatively correlated with NK cell infiltration. Finally, molecular docking showed that AgNPs-PVP interacts highly with the target proteins.

AgNPs cause alterations in cell viability. Furthermore, the deregulation of hub genes and the modulation of the immune system are associated with anticancer effects, and molecular docking demonstrated high interaction with the target proteins that should be studied experimentally.

Mushrooms are shown to protect against the side effects of cancer. Therefore, mushrooms with proven anticancer properties and active ingredients are fascinating in the search for new cancer drugs.

In this study, the effects of extracts from Hericium coralloides (M1), Lactarius deliciosus (M2), Lepista nuda (M3), Pleurotus ostreatus (M4), and Suillus collitinus (M5) together on HCT116 were investigated. Mesenchymal stem cells (MSCs) were used to study the effect on healthy cells.

MTT was used to determine cell viability. Dose-response curves were generated, the IC50 values of the compounds were calculated, and the effect of the extracts was compared using it. The FTIR was used to analyze the quantitative changes of the cellular components.

The evaluation of the IC50 values of all fungal species showed that they reduced the cell viability of HCT116 cells. In contrast, no significant reduction in cell viability was observed in MSCs. Changes in the ratio of cell membrane lipids, proteins, and cell nucleic acids between control and fungal-treated HCT116 cells were detected by FTIR. Many of the chemotherapeutic agents are of plant origin, and many resources should still be explored to inhibit the side effects of cancer therapy.

The data obtained through this experiment will serve as a reference for studies to be a new source of anticancer drugs in modern pharmacology.

Diabetic Nephropathy (DN) is the leading cause of the end-stage renal disease (ESRD). Finerenone (with the molecular formula C21H22N4O3) is an oral non-steroidal mineralocorticoid antagonist (ns-MRA) that is both highly potent and has strong selectivity for the MR. At present, it has been used to treat DN. However, the molecular mechanism of finerenone in the treatment of diabetic nephropathy remains unclear.

In this study, we employed bioinformatics approaches to investigate the molecular mechanism of finerenone as a novel therapeutic agent for the treatment of DN.

We examined a number of databases, including GEO, DisGeNET, Genecards, and OMIM, to find putative genes linked to DN. We then employed the PubChem database and PharmMapper service platform to identify targets of finerenone. Further analysis was conducted using the DAVID database for enrichment analysis and the STRING database for protein-protein interaction (PPI) networks. Molecular docking (MD) was performed using AutoDockTools software, and results were visualized using PyMOL software.

In total, we identified 82 drug-disease targets, primarily associated with lipid and atherosclerosis, diabetic cardiomyopathy, MAPK signaling pathway, and PI3K-Akt signaling pathway. Our PPI network analysis and docking studies demonstrated good binding ability of finerenone to specific targets such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.

Finerenone has the potential to reduce the progression of DN through various pathways, including lipid and atherosclerosis, diabetic cardiomyopathy, MAPK signaling pathway, and PI3K-Akt signaling pathway. Moreover, it could exert anti-inflammatory and antifibrotic effects on specific targets, such as AKT1, MMP-9, IGF1, EGFR, CASP3, PPARG, ESR1, MMP-2, and KDR.

Ionic immobilized liquids and multi-component reactions are integral to green chemistry, facilitating the synthesis of biologically active compounds, such as xanthene and acridine derivatives. These approaches have garnered significant attention in recent years.

The aim of this study was to synthesize novel xanthene and acridine derivatives with diverse substituents and heterocyclic rings. Furthermore, the research sought to evaluate their anticancer activity against various cancer cell lines and analyze their structure-activity relationships (SAR) to determine how structural modifications impact their biological effectiveness.

The core compounds in this study were synthesized from cyclohexane-1,3-dione and triethoxymethane under two distinct reaction conditions. The first involved the use of a solvent with either Et3N or NH4OAc as a catalyst, while the second employed a solvent-free approach using an ionic liquid catalyst (ILs).

The anti-proliferative activity of all synthesized compounds was evaluated against six selected cancer cell lines, revealing that many compounds exhibited significant inhibitory effects. Furthermore, their inhibitory potential against tyrosine kinases and Pim-1 kinases was assessed, along with an investigation of their mechanism of action on tyrosine kinases.

The anti-proliferative activity of the newly synthesized compounds was evaluated against six cancer cell lines. Many of the compounds exhibited strong inhibitory effects not only against the tested cancer cell lines but also against tyrosine kinases and Pim-1 kinases.

Advances in nanotechnology have revealed innovative applications in pharmaceutical sciences to solve unmet medical needs. Over the past decades, antibiotic resistance has emerged as a global concern. This catastrophic phenomenon, with a rapid increase in frequency, indicates the urgent need for the introduction of new approaches. In this respect, as a class of inorganic nanomaterials, mesoporous silica nanoparticles (MSNs) are of interest. Amongst, MCM-41 (MCM-Mobil Composition of Matter) possesses many advantages suitable for biomedical applications such as high pore volume, large surface area capacity, and controlled release properties as well as high bioavailability.

In the current study, we aimed to develop a new drug delivery platform of ciprofloxacin (CIP) to combat antibiotic resistance practically using MSNs.

The MCM-41 nanoparticles were synthesized using surfactant as the templating agent. Afterward, drug molecules were loaded in the prepared mesoporous structure, and several experiments were conducted to assess physicochemical properties. As well, the encapsulation efficiency, release profile, and antibacterial properties were also evaluated.

The CIP-loaded MCM-41 (CIP@MCM-41) nanoparticles represented good physicochemical properties. The results of the DLS method showed a particle size of 93.73 nm with a low polydispersity index (PDI) of 0.21, while SEM imaging demonstrated spherical particles with relative shape uniformity and size distribution. The encapsulation efficacy of MCM-41 MSNs for CIP was measured to be 28.7% ± 0.37 followed by negligible changes over 60 days. The release profile of CIP from prepared nanoparticles was also demonstrated to follow the zero-order kinetic model. Moreover, CIP@MCM-41 nanoparticles exhibited high antibacterial properties against test microorganisms (Escherichia coli, Klebsiella pneumoniae, Staphylococcus epidermidis, and Micrococcus luteus).

The current formulation could be a promising candidate for the delivery of therapeutic agents to combat antibiotic resistance and promote public health.

A mechanism has been proposed for the targeted transfer of an antimalarial drug, which involves 1, 2, and 4 trioxane (TRX) reagents. The trioxane ring is sensitive to ferrous iron, Fe)II(, and when exposed to it, it breaks down into smaller pieces, releasing the antimalarial drug mML (a mock form of DPA1 inhibitor ML4118S).

The oxane ring is attached to a nanoparticle called adamantane, which helps facilitate the reaction. The mechanism has been investigated using two reactants: TRX-R-mML and TRX-H-mML complexes (R is a side chain). The researcher used the transition state theory, the Hartree-Fock level (HF), and the ground state series 6-31G** to investigate the mechanism. The physicochemical and geometric properties of the components involved in the reaction were measured to explain the mechanism better.

The results indicate that the R as a side chain significantly affects the mentioned mechanism and properties. Additionally, the results of the calculations show the stability of the complexes required as reactants in the reaction.

The TRX-mML-R complex has more strength, and polarity than TRX-mML-H, and the energy level of the transition state of TRX-mML-R is lower than that of TRX-mML-H, indicating faster passage of raw materials.