Current Medicinal Chemistry - Volume 33, Issue 2, 2026

Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown.

In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11.

Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration.

In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

ZNF280A, a pivotal member of the zinc finger protein family, is significantly involved in vital cellular functions including cell proliferation, programmed cell death, cellular invasion, metastasis, and resistance to therapeutic drugs across various malignancies. However, its comprehensive role in pan-cancer has not been thoroughly investigated.

This research aims to elucidate the oncogenic and immunological functions of ZNF280A across different types of cancer. We conducted an extensive analysis of ZNF280A expression levels, prognostic significance, functional pathways, methylation status, and interactions with immune cells, while also examining immune infiltration patterns and responses to immunotherapy using diverse databases.

Our findings reveal that ZNF280A expression is significantly upregulated in numerous cancers, correlating with adverse patient prognosis. This association appears to be linked to its involvement in key cancer-related pathways, including the Ras signaling pathway, and its correlation with ZNF280A methylation levels, microsatellite instability (MSI), tumor mutational burden (TMB), and the dynamics of immune cells. Notably, ZNF280A seems to undermine anti-tumor immunity and the effectiveness of immunotherapeutic approaches by promoting the infiltration of immune cells and compromising the functionality of cytotoxic T lymphocytes.

These findings suggest that ZNF280A holds promise as a valuable indicator for forecasting patient outcomes and assessing the effectiveness of immunotherapy, thereby opening avenues for further exploration into targeted therapeutic approaches.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, but no drugs can cure this disease. Chalcones possess good antioxidant activity, anti-neuroinflammatory activity, neuroprotective effects, inhibitory effects on Aβ aggregation, and Aβ disaggregation ability. Therefore, chalcones are ideal lead compounds, and the discovery of novel anti-AD agent-based chalcones is necessary.

Hydroxy groups and aryl benzyl ether groups were introduced into chalcone scaffolds to obtain a series of 2-hydroxyl-4-benzyloxy chalcone derivatives. These derivatives were further synthesized, biologically evaluated, and docked.

Most target derivatives exhibited good anti-AD activities. In particular, compound 11d had excellent inhibitory effects on self-induced Aβ1-42 aggregation (90.8% inhibition rate at 25 μM) and Cu²⁺ induced Aβ1-42 aggregation (93.4% inhibition rate at 25 μM). In addition, it also exhibited good Aβ1-42 fibril disaggregation ability (64.7% at 25 μM), significant antioxidative activity (ORAC = 2.03 Trolox equivalent), moderate MAO-B inhibition (IC50 = 4.81 μM), selective metal chelation, appropriate BBB permeation, and dramatic anti-neuroinflammatory ability. In addition, compound 11d relieved AD symptoms and protected hippocampal neurons in vivo.

Compound 11d is a promising multifunctional anti-Aβ agent.

Highly sensitive, accurate, and low-cost detection systems are gaining interest for early intervention in the progression of Alzheimer's disease (AD). Amyloid-beta (Aβ), a peptide highly involved in the progression of AD, is found in abundance in patients with severe AD.

This research focused on developing an Aβ oligomer (AβO) biosensor using a single-walled carbon nanotube-modified (SWCN) interdigitated electrode (IDE) sensor.

The SWCN was functionalized onto the sensor surface through an amine linker, followed by the attachment of an aptamer-gold nanoparticle (GNP) complex, which was used to capture the AβO.

The GNP-aptamer was saturated at 500 nM on the SWCN surface, and AβO was detected using a sandwich consisting of aptamer-AβO-antibody. The SWCN modification increased the number of aptamer attachment sites on the IDE, while the aptamer and antibody conjugation with GNP enhanced AβO interaction. This sandwich assay detected AβO at concentrations as low as 10 fM, with a linear regression coefficient (y = 2.9189x - 2.076; R² = 0.9544). Furthermore, AβO-spiked artificial CSF was detected without interference, as confirmed by the increased current responses. No significant changes were recorded with control proteins, including α-synuclein, IgG antibody, and a complementary aptamer, indicating specific AβO detection.

This SWCN modified IDE-based sandwich detects AβO at its lower level and contributes to the early diagnosis of AD.

Hyperuricemia (HUA) is a condition characterized by excessive uric acid production and/or inadequate uric acid excretion due to abnormal purine metabolism in the human body. Uric acid deposits resulting from HUA can lead to complications such as renal damage. Currently, drugs used to treat HUA lack specificity and often come with specific toxic side effects.

This study aimed to investigate the renal protective effects of an optimized tea polyphenol formula and allopurinol in a rat model of hyperuricemia following renal resection. The goal was to explore the mechanisms underlying these effects.

Initially, a blend was formulated based on the distinctive functions of catechins, thearubigins, tea polysaccharides, and theanine. Orthogonal experiments were then employed to select a rational combination. A 5/6 renal resection rat model was successfully established, and the animals were fed a 2% oxonic acid diet to induce hyperuricemia. Urinary protein content was measured using the biuret method, and serum levels of uric acid, creatinine, and urea nitrogen were determined biochemically. Kidney pathology was examined through HE staining and renal tubulointerstitial pathological scoring. The expression of α-SMA, CD34, PCNA, and TGF-β in renal tissue was detected using immunohistochemistry. Apoptosis of renal tubular epithelial cells was assessed using the TUNEL method.

Hyperuricemia markedly worsens renal damage in rats following nephrectomy, while tea polyphenols demonstrate the ability to reduce levels of blood uric acid, urea nitrogen, creatinine, and urinary protein. Additionally, tea polyphenols enhance smooth muscle proliferation in renal glomerular arterioles, prevent the loss of interstitial capillaries, alleviate apoptosis of renal tubular epithelial cells, promote their proliferation, and reduce interstitial fibrosis. A significant improvement in the severity of renal damage is observed in rats subjected to nephrectomy combined with hyperuricemia, and this effect surpasses that of allopurinol.

Tea polyphenols could effectively alleviate renal damage in rats with nephrectomy combined with hyperuricemia. They demonstrate high cost-effectiveness and minimal side effects, positioning them as a promising new therapeutic option for hyperuricemia-induced renal damage.

Necroptosis is a modifiable form of cell death mainly dependent on RIPK3 and MLKL. The association between necroptosis and inflammation has been a key focus of research. An increasing number of studies have shown that necroptosis plays an important role in inflammatory diseases, such as inflammatory bowel disease.

Articles published up to 2023 were searched on the Web of Science. VOSviewer, CiteSpace, Gephi, and Microsoft Office Excel were used for bibliometric analysis and visualisation. In addition, journal impact factors and journal partitions were obtained through the Web of Science.

A total of 3011 articles were included in this study. The number of publications and citations in the field increased year by year. China had the highest number of publications. Cell Death & Disease published the most papers in the field. P. Vandenabeele is one of the most important scholars in this field. The most cited reference was “Molecular Mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death”.We found substantial evidence that acute kidney injury, sepsis, cancer, and other diseases are closely related to necroptosis. In addition, we found that inhibitors of necroptosis have great potential in the treatment of inflammatory diseases.

This is the first bibliometric analysis of studies related to necroptosis in inflammatory diseases. Our results provide an overview of basic and influential research, providing a basis for the identification of valuable research directions. Furthermore, this work offers general insight into the role of necroptosis in inflammatory human diseases.

Fat grafting procedures for body contouring and cosmetic reconstruction have received widespread attention.

In recent years, there has been an increase in post-fat grafting infections caused by Mycobacterium abscessus (MA), and there is a lack of representative and standardized murine models of infection; therefore, there has been limited research on the treatment of post-fat grafting MA infections. To overcome this challenge, we constructed an MA infection model after fat grafting.

By evaluating skin charge, dermatopathology, and inflammatory markers, we found that the fat graft + 1×10⁹ CFU/mL bacterial suspension infection group had significant inflammatory symptoms and elevated inflammatory factors on postoperative day 10.

The model construction process was simple and reproducible, which paves the way for further studies on the impact of MA pathogenesis and the efficacy of new treatments.

Myocardial infarction (MI) is a common critical syndrome in the late development of cardiovascular diseases (CVDs), and traditional Chinese Medicine (TCM) treatment has become an essential branch in this field.

This study aimed to use bibliometric methods to examine the research trajectory of TCM treatment of MI from 2007 to 2024 from a multidimensional perspective and analyse its characteristics, hotspots, and frontiers.

This study used the search formula TS OR TI OR AB OR A (“traditional Chinese medicine” or “Chinese medicine” or “TCM” or “traditional medicine, Chinese” or ” Chinese traditional medicine” or “Chinese medicine, traditional”) AND TS OR TI OR AB OR AK (“myocardial infarction” or “myocardial infarctions” or ” infarction, myocardial” or “infarctions, myocardial” or “myocardial infarct” or “MI”) to find the Web of Science Core Collection (WOSCC) of relevant studies from 01/01/2007 to 04/29/2024. Target literature records were analysed and graphed using CiteSpace, VOSviewer, and Scimago Graphica.

A total of 754 records were obtained and 399 records were finally retained after screening. Countries, institutions, authors, and journals were visually analyzed. The current research hotspots and frontiers included Salvia miltiorrhiza, ischemia-reperfusion injury, pathway, molecular docking, and network pharmacology.

This research study would enrich the researchers' understanding of the existing research methodology and future development trends and provide a more efficient research methodology for the research on the mechanism of action of TCM for the treatment of MI and its clinical trials.

Fructose, like other sugars and sugar metabolites, is capable of glycating protein. Insulin's fructosylation leads to the generation of Advanced Glycation End Products (AGEs). Reducing sugars reaction with proteins to form Schiff’s bases, which are characterized by the presence of an imine (C=N) bond. The Schiff bases then undergo irreversible rearrangements, followed by the production of much more stable compounds called Amadori products. These Amadori products can further undergo oxidation, dehydration, cyclization, and condensation to form highly toxic advanced glycation end-products (AGEs). These processes are accompanied by oxidative stress, secondary structural perturbations, and altered morphology, progressing toward amyloidogenesis. Metformin, a biguanide, is the most common drug used to treat type 2 Diabetes Mellitus (T2DM).

The aim of this study was to evaluate the protective effect of metformin against fructosylation-induced cross-β structures and amyloid aggregations of human insulin.

UV-absorbance and fluorescence spectroscopy, determination of carbonyl content, free lysine and arginine residues, determination of fructosamine content, SDS-PAGE, circular dichroism (CD) spectroscopy, dynamic light scattering, and scanning and transmission electron microscopy.

Physicochemical studies in the presence or absence of metformin revealed a concentration-dependent structural restoration of fructosylated insulin. Results from the thioflavin-T fluorescence assay suggested that metformin limited the transition of insulin from native to fibrillar state, which was validated by scanning and transmission electron microscopy. Metformin lowered the ThT fluorescence intensity in a concentration-dependent manner. The ThT-specific fluorescence intensity was reduced to 114 and 112.5%. The fluorescence intensity at 2.5 mM metformin was close to native insulin. Electron microscopy revealed that insulin fructosylated by 25 mM fructose in the presence of 2.5 mM metformin suppressed the formation of fibrillar structures. Dynamic light scattering data revealed the potential of metformin to conserve and reinstate the increased hydrodynamic radii (Rh) of fructosylated insulin close to the native conformer. The Rh values of native, fructosylated insulin and insulin incubated with fructose and metformin were found to be 2.65 ± 0.28, 307.6 ± 24.19 nm, and 110.1 ± 4.08 nm, respectively. This study also identified metformin as an antioxidant by protecting critical amino acid residues of the insulin domain.

The study reports the protective effects of metformin on insulin structure, conformation, and function. The findings suggest a potential role for metformin in improving the risk profile associated with insulin resistance due to altered structure or the accumulation of protein aggregates. Interaction studies between insulin and metformin presented here are due to the chemical effect; hence, further in-depth studies are required to identify the molecular mechanism of insulin sensitivity and changes in cellular processes and pathways.

The results suggest that metformin safeguards against fructosylation-induced structural, conformational, morphological, and amyloidogenic aggregating tendencies of insulin. Protein aggregation has been linked to several neurological and metabolic diseases. Hence, metformin may be crucial in preserving the biological activity of insulin by maintaining and protecting its structural integrity and minimizing the associated comorbidities. The study may further be extended to identify the role of metformin in controlling the gradual insulin resistance in T2DM at the molecular level.

Synthesis and in silico therapeutic potential of newly synthesized amide derivatives based on bis((4-amino-4-oxobutanoyl)oxy)zinc scaffold and their antidiabetic potential.

Indeed, the design and synthesis of coordinated complexes are gaining substantial attention in synthetic chemistry due to their intriguing structures and possible applications in catalysis, molecular magnetism, and biological potentials.

The current study deals with the synthesis of amide derivatives based on bis((4-amino-4-oxobutanoyl)oxy)zinc scaffold C1–C5 followed by Swiss absorption, distribution, metabolism, and elimination (ADME), Density functional theory (DFT) studies, molecular docking and in vitro anti-diabetic activity.

The structure of newly derived compounds was characterized using physiochemical properties and spectroscopic techniques. SwissADME web service was used to analyze the physicochemical properties of the synthesized compounds. The electronic characteristics of C1-C5 were examined using the Time-dependent density functional theory (TD-DFT) approach. Further α-glucosidase and α-amylase enzymes analyzed the anti-diabetic potentials of the synthesized compounds at various concentrations.

SwissADME analysis of compounds showed deviation from Lipinski's rule of five, which is a critical marker in drug development. It predicated poor permeability and absorption in blood brain barrier, while the bioavailability score indicates a suitable plasma concentration. Compounds are assumed to have straightforward synthesis steps. The TD-DFT study found that the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) were concentrated on the π-conjugated system of the substituted rings, indicating a significant delocalization of electrons. The study also found that compounds possess chemical hardness and stability properties, with a lower electrophilicity index indicating higher bioactivity and lower toxicity and thus, potential as drug candidates. In in vitro activity, compound C-2 displayed excellent inhibition against both enzymes with IC50 values 2.23 and 2.63 μM, respectively.

In short, the newly synthesized amide derivatives based on bis((4-amino-4-oxobutanoyl)oxy)zinc scaffold C1–C5 possess promising in silico efficacy, stability and safety with variable pharmacokinetic profile and anti-diabetic potentials, therefore, further studies are needed.