Saad Alqarni

Medicinal plants serve as critical reservoirs of bioactive scaffolds for targeted cancer therapeutics. This study evaluated the antiproliferative potential of Carpobrotus edulis methanolic flower extract across a panel of human cancer cell lines, including pancreatic (Panc-1), breast (MCF-7), liver (HepG-2), and lung (A-549) malignancies. Screening assays revealed potent, dose-dependent cytotoxicity in an MTT-based viability assay, with A-549 lung cancer cells being the most sensitive of the four tested cancer cell lines (IC₅₀ = 3.62 ± 0.34 μg/mL). Selectivity over non-malignant cells was not assessed. Flow cytometry showed an increase in the S-phase fraction and in Annexin V-positive cells, and ELISA showed higher Bax and p53 and lower Bcl-2 in extract-treated A-549 cells, consistent with apoptosis through the intrinsic pathway. The measured caspase-3 concentration was lower after treatment, and the assay does not distinguish pro-caspase-3 from cleaved caspase-3. Phytochemical profiling via GC-MS identified a diverse array of bioactive metabolites, predominantly triterpenoids, phytosterols, fatty acid derivatives, and cyclitols. To explore EGFR as a putative target, an in vitro EGFR kinase assay was combined with molecular docking and molecular dynamics (MD) simulations. Among the profiled metabolites, the cyclitol derivative mome inositol displayed the most favorable docking score binding affinity toward the EGFR kinase domain (−7.35 kcal/mol), establishing robust hydrogen-bonding networks with key catalytic residues within the active site. Furthermore, a 100 ns MD simulation revealed the relative thermodynamic stability of the mome inositol–EGFR complex with more favorable RMSD, RMSF, hydrogen bond and radius of gyration profiles than the co-crystallized reference ligand. Collectively, these integrated in vitro, phytochemical, and in silico findings indicate that methanolic extract of C. edulis flowers exerts potent anticancer activity predominantly through mitochondrial-mediated apoptosis complemented by a computationally predicted interaction between its major cyclitol constituent and the EGFR kinase domain. These results establish the extract as a promising early-stage anticancer lead and provide a clear rationale for advancing to mechanistic studies, with in vivo validation reserved for subsequent investigations.

Cancer remains the foremost cause of death globally and presents a major obstacle to increasing life expectancy. The identification of natural anticancer agents is therefore a key research priority. Essential oils (EOs), widely used in traditional medicine, possess diverse biological activities that warrant systematic investigation. Anisosciadium orientale is traditionally regarded as a safe, edible herb; however, its therapeutic potential has not been extensively explored. In this study, the chemical profile of the EO obtained from the aerial parts of A. orientale was characterized using GC–MS analysis. Antioxidant activity was evaluated through hydrogen peroxide and ABTS radical-scavenging assays, whereas anticancer effects and underlying mechanisms were evaluated in multiple cancer cell lines using MTT cytotoxicity assays, flow cytometry, and molecular docking studies. Sixty constituents were identified in the EO, with myristicin and its isomer among the major components. The EO exhibited notable antioxidant and anticancer activities, demonstrating cytotoxicity against lung carcinoma A549 cells with an IC₅₀ of 84.8 µg/mL and inducing significant apoptosis accompanied by G₂/M cell-cycle arrest. Treatment with the EO markedly boosted levels of caspase-3, p53, Bax, and the Bax/Bcl-2 ratio, while downregulating Bcl-2 expression. Molecular docking revealed strong binding affinities of major constituents—particularly myristicin and its isomer—toward the EGFR kinase active site, suggesting a high degree of complementarity with the EGFR kinase domain. Collectively, this study represents the first comprehensive study integrating chemical profiling, in vitro cytotoxicity, mechanistic assays, and molecular docking for A. orientale. These findings position A. orientale EO as a promising scaffold for the development of natural anticancer interventions, providing a foundation for future preclinical exploration.

Background and Objectives: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, yet its molecular basis remains unclear. Nicotinamide adenine dinucleotide (NAD⁺) metabolism is crucial for energy regulation, redox balance, and inflammation. This study investigated the dysregulation of key NAD⁺ salvage enzymes (CD38, NAMPT, and SIRT1) across albuminuria stages in type 2 diabetes (T2D). Materials and Methods: A cross-sectional study was conducted on 225 participants: healthy controls (n = 45), T2D with normoalbuminuria (n = 60), microalbuminuria (n = 60), and macroalbuminuria (n = 60). Serum CD38, NAMPT, and SIRT1 were measured by ELISA, while CD38 and SIRT1 gene expression in peripheral blood mononuclear cells was analyzed by qPCR. Results: CD38 and NAMPT levels increased progressively with albuminuria, whereas SIRT1 levels declined significantly. CD38 and NAMPT correlated positively with HbA1c, creatinine, and urinary albumin-to-creatinine ratio (UACR), while SIRT1 showed inverse correlations and a positive association with eGFR. Regression analysis identified CD38 and NAMPT as independent positive predictors of albuminuria, and SIRT1 as a negative predictor. ROC analysis revealed strong diagnostic performance for CD38 (AUC = 0.89) and SIRT1 (AUC = 0.88). Conclusions: These findings highlight disrupted NAD⁺ salvage pathways in DN and suggest that restoring NAD⁺ balance, through CD38 inhibition, SIRT1 activation, or NAD⁺ precursor supplementation, may offer promising renoprotective strategies.

Influenza A virus (IAV) is a zoonotic pathogen responsible for seasonal and pandemic flu. The extensive genetic and antigenic diversity within and between IAV phylogenetic groups presents major challenges for developing universal vaccines and broad-spectrum antiviral therapies. Current interventions provide limited protection due to the virus’s high mutation rate and capacity for immune evasion. Recent advancements in viral hemagglutinin (HA)-targeting small-molecule entry inhibitors offer a promising avenue to overcome these limitations. Here, we present structural and functional analyses of two group 2 HA-specific small-molecule inhibitors recently identified by our team. Cryogenic electron microscopy (cryo-EM) structures revealed that these inhibitors bind a conserved pocket within the HA stalk, likely interfering with the conformational rearrangements necessary for membrane fusion and viral entry. Structure-guided mutagenesis confirmed the critical roles of key interacting residues and uncovered distinct resistance profiles between the two compounds, as well as in comparison to Arbidol, a previously reported HA inhibitor. Notably, our structural analysis highlights intrinsic barriers to achieving cross-group inhibition with current small-molecule designs. To address this, we propose an alternative strategy for broadening antiviral coverage. Together, these findings provide mechanistic insights into IAV entry inhibition and a foundation for the rational design of next-generation anti-influenza therapeutics.

The evergreen coniferous tree Thuja occidentalis is a member of the Cupressaceae family. This study included biological, cytotoxic, and in silico docking analyses in addition to a phytochemical composition analysis of the plant leaves and stem ethanolic extracts. The extracts’ in vitro cytotoxicity efficacy against various cancer cell lines was examined. Additionally, certain phytochemical compounds were identified by gas chromatographic analysis and subsequently assessed in silico against anticancer molecular targets. Also, their antiviral effect was assessed. Good cytotoxic activity was demonstrated by plant extracts against the lung and colorectal cancer cell lines. With half-maximal inhibitory concentration values of 18.45 μg/mL for the leaf extract and 33.61 μg/mL for the stem extract, apoptosis and S-phase arrest was observed in the lung cancer cell line. In addition, the leaf extract demonstrated effective antiviral activity, with suppression rates of 17.7 and 16.2% for the herpes simplex and influenza viruses, respectively. Gas chromatographic analysis revealed the presence of relevant bioactive components such as Podocarp-7-en-3β-ol, 13β-methyl-13-vinyl, Megastigmatrienone, and Cedrol, which were tested in silico against anticancer molecular targets. Our findings suggest that plant ethanolic extracts may have potential therapeutic uses as anticancer drugs against lung cancer in addition to their antiviral properties, which opens up further avenues for more investigation and applications.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds—CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

The influenza A virus (IAV) is a highly contagious virus that causes pandemics and seasonal epidemics, which are major public health issues. Current anti-influenza therapeutics are limited partly due to the continuous emergence of drug-resistant IAV strains; thus, there is an unmet need to develop novel anti-influenza therapies. Here, we present a novel imidazo[1,2-a]pyrimidine scaffold that targets group 2 IAV entry. We have explored three different regions of the lead compound, and we have developed a series of small molecules that have nanomolar activity against oseltamivir-sensitive and -resistant forms of group 2 IAVs. These small molecules target hemagglutinin (HA), which mediates the viral entry process. Mapping a known small-molecule-binding cavity of the HA structure with resistant mutants suggests that these molecules bind to that cavity and block HA-mediated membrane fusion.