Current Medicinal Chemistry[JOURNAL]
Sun
200 papers
Clinical Significance of HBOT in Hypoxia-Induced Pathophysiological Conditions: A Comprehensive Investigative Study.
Bhargava R, Bhardwaj K, Oleksak P … +1 more , Kuca K
Curr Med Chem · 2026 Apr · PMID 41968551 · Publisher ↗
Hyperbaric oxygen therapy involves breathing pure oxygen at high pressure (around 2-2.5 atmospheres), leading to increased blood oxygen levels in tissues. The therapeutic efficacy of hyperbaric oxygen therapy (HBOT) is o...
Hyperbaric oxygen therapy involves breathing pure oxygen at high pressure (around 2-2.5 atmospheres), leading to increased blood oxygen levels in tissues. The therapeutic efficacy of hyperbaric oxygen therapy (HBOT) is often dose-dependent, correlating with the number of applications, particularly within hypoxic tissues. HBOT provides neuroprotection following central nervous system trauma and serves as a critical intervention for non-neurological conditions, including Fournier's gangrene, chronic osteomyelitis, and carbon monoxide poisoning. It has also been applied as an adjunctive treatment in surgical site infections, radiation-induced tissue damage, and, more recently, in COVID-19-associated hypoxemia. HBOT enhances recovery in hypoxic and ischemic tissues; relative contraindications such as uncontrolled hypertension and untreated ulcers require careful consideration. Current applications of HBOT are guided by evidence- based protocols established by international and national hyperbaric medicine associations such as the Undersea and Hyperbaric Medical Society (UHMS) and the European Underwater and Baromedical Society (EUBS). In this review, we have discussed the properties of HBOT and explored in depth the physiological relevance of oxygen in the treatment of several disorders, based on clinical evidence, including current indications and underlying mechanisms. HBOT has demonstrated promising outcomes in neurological and neuropsychological disorders, with reports of improved neuronal activation, cognitive performance, and functional recovery in both acute and chronic disease patients. In clinical reports, HBOT was found to be effective in activating nerves and treating neuropsychological disorders in both non-chronic and chronic disease patients.
Cold-Induced Gouty Arthritis: Exploring the Pathophysiological Link between Hyperuricemia and Gout Flare Triggers.
Lin Z, Goel A, Faizi FR … +4 more , Maqbool M, Chen S, Kumar K, Sharma A
Curr Med Chem · 2026 Apr · PMID 41968550 · Publisher ↗
Cold temperatures have been recognized as a possible catalyst for gouty arthritis exacerbations in individuals with hyperuricemia. The mechanisms underlying cold-induced gout are, however, minimally recognized. The artic...
Cold temperatures have been recognized as a possible catalyst for gouty arthritis exacerbations in individuals with hyperuricemia. The mechanisms underlying cold-induced gout are, however, minimally recognized. The article examines the pathophysiological connection between hyperuricemia and cold-induced gout flare triggers, emphasizing the molecular and physiological mechanisms involved. Genetic predisposition significantly influences an individual's risk of developing hyperuricemia and subsequent gout, underscoring the relevance of genetic variables in disease susceptibility. The diagnosis of gout depends on a combination of laboratory testing, such as blood uric acid levels, synovial fluid examination for urate crystals, and imaging to evaluate joint damage. Cold exposure is a significant environmental element that promotes the crystallization of monosodium urate in synovial fluid, initiating an inflammatory response. Activating the NLR family pyrin domain-containing 3 (NLRP3) inflammasome triggers the production of pro-inflammatory cytokines, consequently contributing to the pathophysiology of gout flares. The NLRP3 inflammatory system gets activated, leading to the secretion of pro-inflammatory cytokines. Low temperatures additionally impair blood circulation and the efficacy of immune cells, hence exacerbating inflammation. This review highlights the recent findings on epidemiology, pathophysiology, and diagnostic techniques of gouty arthritis, providing insights into prospective preventive strategies, therapies for those affected, and offering hope for the future. Overall, it provides an overview of the mechanisms behind cold-induced gout flares.
Poly Beta-Amino Esters Nanoparticles as a Promising Strategy for Colon Cancer Therapy: Covering Synthesis Mechanisms, Characterization, Preclinical and Clinical Progress, and Regulatory Challenges.
Shingare A, Bhattacharya S
Curr Med Chem · 2026 Apr · PMID 41968549 · Publisher ↗
Colon cancer is still one of the biggest health challenges globally, and most of the available treatments are hindered by drug resistance, systemic toxicity, and suboptimal efficacy. The Poly (beta-amino esters) (PBAE)-b...
Colon cancer is still one of the biggest health challenges globally, and most of the available treatments are hindered by drug resistance, systemic toxicity, and suboptimal efficacy. The Poly (beta-amino esters) (PBAE)-based nanoparticles have emerged as a promising nanotechnology-driven solution to these challenges. This review begins with the synthesis and functionalization of PBAE nanoparticles by focusing on polymerization techniques, targeting strategies, and scalability for clinical applications. The physicochemical properties of these nanoparticles, such as particle size, surface morphology, zeta potential, stability, biodegradability, and drug loading efficiency, are discussed in relation to their impact on therapeutic performance. Mechanistic insights into drug encapsulation, controlled release, tumour targeting, and the potential to overcome Multidrug Resistance (MDR) are also provided. Mechanistic insights are provided, including hydrophobic interaction-based drug encapsulation for efficient drug loading, pH-responsive controlled release in acidic tumor microenvironments, receptor-mediated tumour targeting using surface-functionalized ligands, and strategies to overcome Multidrug Resistance (MDR). Thereafter, preclinical studies are assessed, which include in-vitro cytotoxicity experiments and in-vivo animal models that test for efficacy, pharmacokinetics, and biodistribution. The review will then assess the status of PBAE nanoparticles in clinical trials, focusing on safety, efficacy, and the effects on patient outcomes in colorectal cancer treatment. Finally, regulatory approval, toxicity assessments, and commercialization challenges are discussed along with recommendations for overcoming these barriers. The review concludes by highlighting advancements in nanoparticle design, emerging therapeutic strategies, and the future potential of PBAE nanoparticles to transform colorectal cancer treatment.
Novel Indole Derivatives as SRC/EGFR Inhibitors: Synthesis, Biological Evaluation, and Analysis.
Olgen S, Karaca BT, Kaleli SNB … +2 more , Demirel UU, Ece A
Curr Med Chem · 2026 Apr · PMID 41968548 · Publisher ↗
INTRODUCTION: Recent studies have reported a correlation between SRC and EGFR as key factors contributing to tumor aggressiveness in cancers, such as glioblastoma, colon, breast, and lung cancers. Resistance to therapy r...
INTRODUCTION: Recent studies have reported a correlation between SRC and EGFR as key factors contributing to tumor aggressiveness in cancers, such as glioblastoma, colon, breast, and lung cancers. Resistance to therapy remains a major obstacle in cancer treatment. Therefore, the discovery of novel compounds with inhibitory potential is crucial. In this study, urea- and pyrimidine-containing compounds structurally similar to osimertinib were designed as potential inhibitors of both SRC and EGFR kinases, with the aim of identifying compounds that may also overcome resistance conferred by mutations. METHODS: The compounds were synthesized through the development of new synthetic routes. Their structure-activity relationships (SAR) were evaluated using in vitro enzyme inhibition assays, cell culture experiments, molecular docking, and molecular dynamics studies. RESULTS: Compounds 19, 20, and 21, which bear substitutions at the third position of the indole ring, inhibited SRC kinase with 77.75-89.22% activity. These compounds also demonstrated notable cytotoxicity against the PC3 cell line, with IC values of 7.89, 6.92, and 9.85 μM, respectively, comparable to reference compounds cisplatin (IC = 5.16 μM) and dasatinib (IC = 0.9 μM). Notably, compound 20 was active against both EGFR and SRC kinases, with IC values of 3.91 μM and 0.00058 μM, respectively. Compound 20 also exhibited the strongest cytotoxic effect on prostate cancer cells (IC = 6.92 μM). Further analyses indicated that compound 20 induced apoptosis in cancer cells by increasing the levels of caspase-3, caspase-8, and Bax, while reducing Bcl-2 expression. Molecular docking and dynamics studies revealed strong interactions of compound 20 with the target receptors. DISCUSSION: Docking and biological activity studies indicated that compound 20 (1-(2- Fluoro-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)amino)phenyl)-3- phenylurea) is a promising dual inhibitor of both EGFR and SRC kinases. analyses further support the potential therapeutic efficacy of compound 20. CONCLUSION: Overall, compound 20 emerged as the most promising candidate from this study, warranting further investigation for its therapeutic potential.
Research Advances in the Structural Characterization and Biological Activity Assessment of Neocryptotanshinone.
Wang Y, Li J, Cui S
Curr Med Chem · 2026 Apr · PMID 41968547 · Publisher ↗
Neocryptotanshinone (NCTS), a rare diterpene quinone bioactive compound isolated from Salvia miltiorrhiza, was first reported in 1941 and structurally characterized in 1987. The phenanthraquinone core has been extensivel...
Neocryptotanshinone (NCTS), a rare diterpene quinone bioactive compound isolated from Salvia miltiorrhiza, was first reported in 1941 and structurally characterized in 1987. The phenanthraquinone core has been extensively characterized in terms of structural confirmation and synthesis. Due to its low natural abundance, NCTS is challenging to extract but can be obtained through semisynthesis. Mechanistically, NCTS was identified in 2015 as an inhibitor of the nuclear factor kappa-B (NF-κB) pathway, inducing a cascade of downstream effects. Its low cytotoxicity, minimal induction of cyclooxygenase-2 (COX-2) expression, and other favorable pharmacological properties suggest therapeutic potential. Recent research has focused on NCTS's therapeutic applications. By modulating multiple pathways, it exerts beneficial effects on heart failure, myocardial ischemia/ reperfusion injury, cerebral ischemia, and type 2 diabetes mellitus. Pharmacokinetic studies are progressing; its promising bioavailability and absorption kinetics require validation. This review summarizes research progress on NCTS and its derivative 16-Ooleoylneocryptotanshinone, covering structural characterization, synthetic routes, structural modifications, pharmacological activities, traditional Chinese medicine applications, and pharmacokinetics. Our goal is to provide a reference for further development of NCTS, which remains in its nascent research phase.
Role of N-Glycolylneuraminic Acid and N-Acetylneuraminic Acid Glycans in Cancer Diagnosis and Therapeutic Strategies.
Bhattacharya S, Gupta K, Sharma M … +2 more , Mukherjee D, Prajapati B
Curr Med Chem · 2026 Apr · PMID 41968546 · Publisher ↗
This review examines the function of N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) glycans in cancer diagnosis and treatment, specifically in their interaction with biodegradable polymeric nanop...
This review examines the function of N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) glycans in cancer diagnosis and treatment, specifically in their interaction with biodegradable polymeric nanoparticles. Glycans play a central role in cellular communication, immune response, and adhesion, with structural changes usually indicative of precancerous conditions, thus making them key to diagnostic and therapeutic innovations. Neu5Gc, a dietary non-human sialic acid found in red meat and other foods, becomes a part of cell membranes, evoking immune reactions through anti-Neu5Gc antibodies that promote chronic inflammation, tumour formation, and metastasis. In contrast, Neu5Ac is compatible with human physiology and holds promise in antiviral and genetic disease therapies. This review explores the uses of biodegradable polymeric nanoparticles, including those from natural polymers such as chitosan and alginate, in Neu5Gc targeting for cancer diagnosis, immunotherapy, and drug delivery. It emphasizes their biocompatibility, controlled release, and improved targeting of Neu5Gc-containing tumour antigens. The review also addresses developments in electrochemical biosensors for Neu5Gc detection and computational glycan modeling, highlighting their potential in personalized oncology. By emphasizing biodegradable polymer-based approaches, this research highlights their promise as novel agents for cancer treatment, necessitating continued investigation into glycan-polymer interactions to further improve therapeutic outcomes.
Predicting Clinical Prognosis and Treatment Response in Glioblastoma Based on Gene Replication Stress-Related Features.
Yuan Q, Gao W, Guo M
Curr Med Chem · 2026 Apr · PMID 41968545 · Publisher ↗
INTRODUCTION: Glioblastoma (GBM) is a frequent malignant glioma among astrocytic tumors. Traditional pathological diagnostic criteria inadequately capture the underlying biological heterogeneity, highlighting the need fo...
INTRODUCTION: Glioblastoma (GBM) is a frequent malignant glioma among astrocytic tumors. Traditional pathological diagnostic criteria inadequately capture the underlying biological heterogeneity, highlighting the need for novel biomarkers to improve the diagnostic and prognostic accuracy of GBM. METHODS: Based on the GBM-related data from The Cancer Genome Atlas (TCGA), Replication Stress-related Genes (RSGs) were collected. The RSG feature scores were calculated by ssGSEA and combined with WGCNA to screen target module genes. Enrichment analysis of the modular signature genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Prognostic genes were screened by univariate Cox and multivariate Cox regression analyses to establish a prognostic model for GBM. The Tumor Microenvironment (TME) was assessed using MCPcounter and TIMER methods. Immunotherapeutic responses and drug sensitivity responses were evaluated using the TIDE method. Finally, the role of PDCL3 in GBM was explored via immunohistochemistry, qRT-PCR, wound-healing, and transwell assays. RESULTS: WGCNA identified RSG-associated module genes enriched in DNA replication, DNA-dependent ATPase activity, and other pathways. Four characterized genes (PDCL3, STEAP2, NXPH4, MPST) were selected to establish a Riskscore model for GBM. The risk score of the model was significantly related to the infiltration of myeloid dendritic cells, endothelial cells, and fibroblasts. The Riskscore was significantly positively correlated with the TIDE score, indicating higher immune escape potential in the high-risk group. The high-risk group was sensitive to Vinorelbine and Crizotinib. Through in vitro experiments, it was observed that knocking down PDCL3 noticeably inhibited the viability, migration, and invasion capacities of U87 cells. DISCUSSION: This study validated the correlation between Oncogene-induced Replication Stress (ORS) characteristics and the prognosis of GBM, and screened RSGs to develop a Riskscore for GBM applying multiple types of regression analyses. CONCLUSION: We constructed and verified a four-gene ORS-based prognosis model for GBM, linking replication stress to immune evasion and drug sensitivity for the first time. Experimental validation confirmed the pro-tumorigenic role of PDCL3, offering potential biomarkers and therapeutic targets.
Predicting Clinical Outcomes and Immunotherapy Responses in Lung Adenocarcinoma Based on Nicotine Response Characteristics.
Yue H, Zhou Q, Xu Q … +1 more , Meng S
Curr Med Chem · 2026 Apr · PMID 41968544 · Publisher ↗
INTRODUCTION: Nicotine facilitates the progression of Lung Adenocarcinoma (LUAD) by activating signaling pathways and remodeling the Tumor Microenvironment (TME). However, the molecular classification based on nicotine r...
INTRODUCTION: Nicotine facilitates the progression of Lung Adenocarcinoma (LUAD) by activating signaling pathways and remodeling the Tumor Microenvironment (TME). However, the molecular classification based on nicotine response spectrum and its clinical relevance remained unclear. MATERIALS AND METHODS: We retrieved 52 nicotine response-related genes from the MSigDB database and analyzed RNA-seq data obtained from TCGA-LUAD and GSE31210 cohorts. Distinct molecular subtypes were identified by consensus clustering analysis. Next, differential gene expression analysis and functional enrichment analysis were conducted. A prognostic RiskScore model was constructed using LASSO and Cox regression, and validated via Kaplan-Meier and ROC analyses. Immune microenvironment features were assessed using CIBERSORT, ESTIMATE, and TIDE algorithms, while pathway associations were explored via GSEA. RESULTS: Two distinct molecular subtypes (C1 and C2) were identified, with C1 showing a more favorable prognosis. A RiskScore model developed based on five genes (KCNK1, CPS1, ABCC2, TCN1, PGC) can effectively stratify patients into high- and low-risk groups, with the high-risk group exhibiting a worse overall survival (OS) (p < 0.001). The two risk groups demonstrated distinct enrichment of pathways. Notably, the low-risk group exhibited increased infiltration of regulatory T cells and M2 macrophages and lower TIDE scores, suggesting better immunotherapy response. A nomogram combining RiskScore and AJCC stage demonstrated strong predictive accuracy. DISCUSSION: This study was the first to classify nicotine response-related molecular subtypes for LUAD, offering novel insights into nicotine-driven progression of LUAD. The RiskScore and nomogram may aid in risk stratification and personalized management, though further experimental validation is still needed. CONCLUSION: This study established a nicotine response-related prognostic model for LUAD, revealing its utility in predicting survival and immune therapy responses. Our findings provided novel biomarkers for personalized precision medicine in LUAD.
Non-Coding RNAs and Common Neurosurgical Conditions: A Key to Future Personalized Molecular Therapy.
Gareev I, Beylerli O
Curr Med Chem · 2026 Apr · PMID 41968543 · Publisher ↗
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Single-Cell and Bulk Transcriptomic Integration Reveals a Stemness-Related Astrocyte Subpopulation for Prognostic Risk Stratification in Glioblastoma.
Wang J, Li J, Zhang C … +4 more , Tang C, Miao C, Chen Z, Luo Q
Curr Med Chem · 2026 Apr · PMID 41944114 · Publisher ↗
INTRODUCTION: Glioblastoma (GBM) is an aggressive brain tumor with pronounced heterogeneity. Stemness-related cell subpopulations are crucial for progression and therapy resistance, but their prognostic role remains uncl...
INTRODUCTION: Glioblastoma (GBM) is an aggressive brain tumor with pronounced heterogeneity. Stemness-related cell subpopulations are crucial for progression and therapy resistance, but their prognostic role remains unclear. METHODS: We integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify a stemness-high astrocyte subpopulation. Key genes were selected to construct a prognostic risk model using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, which was validated in The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. Tumor microenvironment and pathway analyses were performed. in vitro functional assays were conducted on GBM cell lines. RESULTS: A four-gene signature (ALDOA, FABP5, TIMP1, and MT1M) was established. The risk model robustly stratified patients into high- and low-risk groups with distinct overall survival in both cohorts. Importantly, multivariate Cox regression confirmed the RiskScore as an independent prognostic factor beyond age and isocitrate dehydrogenase (IDH) mutation status. Functional validation revealed that ALDOA knockdown significantly suppressed GBM cell proliferation and migration in vitro. Further analyses showed that high-risk tumors were characterized by elevated immune/stromal scores, immunosuppressive cell infiltration, and activation of stemness-related pathways, including EGFR/MAPK, NF-κB, and VEGF-mediated angiogenesis. DISCUSSION: This integrated analysis identified a stemness-associated astrocyte subpopulation in GBM. The four-gene signature provides an independent prognostic tool and reflects immune microenvironment remodeling, offering insights into risk stratification and potential targeted therapy. CONCLUSION: We developed a stemness-associated four-gene signature that enables risk stratification in GBM and reveals an immunosuppressive microenvironment in high-risk tumors, providing new directions for prognosis and targeted therapy.
Advances in Nanocarriers for Cancer Treatment: Applications of Halloysite Nanotubes (HNTs) in Solid Tumor Targeted Therapy.
Soltani M, Safaralizadeh R, Rostamzadeh A … +4 more , Hoseinzadeh S, Hosseinpourfeizi MA, Akbari A, Teimourian S
Curr Med Chem · 2026 Mar · PMID 41941169 · Publisher ↗
After a long history of treatments, cancer continues to be one of the most prevalent causes mortalities in worldwide. Chemotherapy, radiotherapy, and surgery are frequently conventional treatments for cancer management,...
After a long history of treatments, cancer continues to be one of the most prevalent causes mortalities in worldwide. Chemotherapy, radiotherapy, and surgery are frequently conventional treatments for cancer management, and provide some benefits; nevertheless, there are plenty of adverse effects, a lack of specificity, considerable off-target effects, and multidrug resistance. These issues led to a challenging situation in solid and liquid tumors. The Nanotechnology approach opens a new and versatile avenue to help scientists in this regard, for example, the delivery of medicinal drugs, which in turn facilitates the targeted cells in a more targeted and tightly controlled manner. Halloysite Nanotubes (HNTs) gained a lot of attention during these years among all of the available nano-carriers because of their special tubular structure, biocompatibility, variable surface chemistry, etc. Using the HNTs simultaneously enhances treatment efficacy and decreases systemic toxicity, making it a good candidate instead of a conventional delivery system that is used in treating solid cancers. Numerous studies have focused on the development of HNT-based nanocarriers for solid tumor therapy. In this review, we want to summarize these recently investigated studies. Subjects considered include mechanisms of action, strategies to overcome tumor-specific barriers, and clinical implications.
The In Vitro Antioxidant, Antibacterial Activities and Cytotoxicity of Mercapto-1,2,4-triazole and their N-Arylacetamide Derivatives Based on Iso- and Terphthalic Acids.
Mhaidat I, Alwedian F, Alzoubi F … +3 more , Almazari R, Almomani W, Batayneh M
Curr Med Chem · 2026 Mar · PMID 41941168 · Publisher ↗
BACKGROUND: Triazole compounds and their acetamide derivatives have received great attention due to their intriguing pharmacological properties. They have become increasingly useful and important in the construction of b...
BACKGROUND: Triazole compounds and their acetamide derivatives have received great attention due to their intriguing pharmacological properties. They have become increasingly useful and important in the construction of bioactive and functional molecules. AIMS: This study aims to report the synthesis and evaluation of a series of new compounds, 5,5'-(1,3- and 1,4-phenylene)bis(4-aryl-4H-1,2,4-triazole-3-thiol) (6a-d) and 2,2'- ((1,3- and 1,4-phenylenebis(4-aryl-4H-1,2,4-triazole-5,3-diyl))bis(sulfanediyl))bis(N-arylacetamide) (7a-p), in terms of their antioxidant, antibacterial, and cytotoxic activities. MATERIALS AND METHODS: Compounds were derived from isophthalic and terephthalic acids. The compounds 6a-d were prepared by reacting the hydrazides of acids with various aryl isothiocyanate, followed by refluxing with potassium hydroxide for 6 hours. Different 2-bromo-N-(4-substitutedphenyl) acetamide 3a-f were prepared by reacting different substituted anilines with bromoacetyl bromide in an aqueous solution of sodium carbonate. The compounds 7a-p were then derived by reacting 6a-d with 3a-f for approximately 30 minutes in an ethanolic solution of potassium hydroxide. The new compounds were fully characterized by 1H-NMR, 13C-NMR, IR spectroscopy, and elemental analysis. ABTS and DPPH assays were performed to investigate the antioxidant and antimicrobial activities of compounds 6a-c and 7a-p, employing the broth microdilution method. The cytotoxicity of the newly synthesized compounds was evaluated using the CCK-8 kit. RESULTS: New compounds of 1,2,4-triazole derivatives 6a-d and their acetanilide derivatives 7a-p were synthesized and were produced with yields ranging from 60% to 93%. Thiol compounds 6a-c exhibited radical scavenging activity. The inhibition percentage increases with increasing concentration of the compounds in both scavenging assays. Most new compounds 6a-c and 7a-p displayed a MIC value of 128 μg/mL against the examined gram-negative and gram-positive bacteria. All new compounds tested in this study were relatively safe in normal cells and did not instigate undesirable toxic effects. DISCUSSION: Structural modification from thiol triazoles (6a-c) to acetanilide-linked derivatives (7a-p) markedly improved antibacterial activity, highlighting the importance of the acetanilide moiety. The moderate antioxidant activity of thiol compounds may result from limited electron donation by the mercapto group, whereas selectivity toward Gramnegative bacteria is likely due to differences in cell walls. The lack of cytotoxicity of the active compounds supports their potential as safe antimicrobial agents. CONCLUSION: New compounds were successfully synthesized with good yield, fully characterized, and proved radical scavenging, moderate antibacterial activity, and showed no undesirable cytotoxicity in normal cells.
A Review of Curcuminoid Derivatives as Next-Generation Depigmenting Agents: Structure-activity Relationships and their Mechanisms.
Fahmi MSAM, Aizan NNFN, Adzahar AN … +2 more , Zolkeflee NKZ, Faudzi SMM
Curr Med Chem · 2026 Mar · PMID 41941167 · Publisher ↗
Hyperpigmentation is a persistent challenge, and current depigmenting agents, such as kojic acid, arbutin, and resveratrol, often exhibit limited efficacy and raise safety concerns. Curcuminoids, a class of natural polyp...
Hyperpigmentation is a persistent challenge, and current depigmenting agents, such as kojic acid, arbutin, and resveratrol, often exhibit limited efficacy and raise safety concerns. Curcuminoids, a class of natural polyphenolic compounds, have emerged as promising scaffolds due to their potent anti-tyrosinase activity and broad inhibitory effects on melanogenesis. This review summarises advances in curcuminoid derivatives and structurally related analogues, including diarylheptanoids, diarylpentanoids, and chalconoids. Key features of the structure-activity relationship (SAR), such as conjugated ketone linkers and para-hydroxyl substitutions, enhance tyrosinase inhibition and modulate melanogenic signalling pathways. Collectively, these insights emphasise the potential of curcuminoid-based scaffolds as safer and more effective next-generation depigmenting agents.
Leveraging Signal Detection and Mendelian Randomization in Spontaneous Reporting for Post-Marketing Surveillance of Drug- Induced Amnesia.
Li C, Chen Y, Yao Y … +1 more , Shang Y
Curr Med Chem · 2026 Mar · PMID 41941166 · Publisher ↗
INTRODUCTION: Drug-induced amnesia is underrecognized due to absence of label indications. This study utilized the FAERS database to identify drugs associated with amnesia and investigated causal relationships through Me...
INTRODUCTION: Drug-induced amnesia is underrecognized due to absence of label indications. This study utilized the FAERS database to identify drugs associated with amnesia and investigated causal relationships through Mendelian randomization (MR) analysis. METHODS: Identification of related drugs from FAERS.corresponding target genes were retrieved from DrugBank. MR analysis, using single-nucleotide polymorphisms as instruments, explored associations between gene expression and amnesia. Molecular docking assessed drug-protein binding, while LASSO and multivariable regression evaluated influencing factors. RESULTS: From 2,731,983 FAERS patients, 58,852 amnesia cases were identified, with 15,038 (0.55%) classified as drug-induced. Drugs such as pregabalin, atorvastatin, gabapentin, and lamotrigine (OR > 1) were linked to increased risk, while age, hypertension, and Tecfidera showed protective effects (OR < 1). MR analysis identified GABBR1, SCN11A, and ADRA2C as significant genetic contributors in blood and brain tissue. Molecular docking revealed stable drug-target binding for lamotrigine (-6.97 kcal/mol), gabapentin (-5.60 kcal/mol), and quetiapine (-7.85 kcal/mol). DISCUSSION: Neuropsychoactive drugs, particularly lamotrigine and gabapentin, demonstrated strong associations with amnesia, implicating mechanisms involving neurotransmitter systems. Variability in drug solubility further influences therapeutic outcomes. Findings emphasize early monitoring for high-risk populations to mitigate amnesic side effects. CONCLUSION: Our study identifies key drugs and genetic markers associated with amnesia. Monitoring programs and personalized risk assessments are essential for improving patient safety and reducing the incidence of drug-induced amnesia. Future research should refine predictive models and explore risk mitigation strategies.
Molecular Mechanism of Long Intergenic Noncoding RNAs in Gastric Cancer.
Latifi-Navid H, Abdi E, Latifi-Navid S
Curr Med Chem · 2026 Mar · PMID 41941165 · Publisher ↗
Long intergenic noncoding RNAs (lincRNAs) are autonomously transcribed noncoding RNAs that, in humans, constitute more than half of all lncRNA transcripts. LincRNAs are distinguished from other lncRNAs by their lack of s...
Long intergenic noncoding RNAs (lincRNAs) are autonomously transcribed noncoding RNAs that, in humans, constitute more than half of all lncRNA transcripts. LincRNAs are distinguished from other lncRNAs by their lack of sequence overlap with coding loci. In addition to originating from evolutionarily conserved enhancer regions, these elements are often located at the boundaries of topologically associated domains. Predominantly localized within the nucleus, lincRNAs play a crucial role in regulating gene expression. They can also be present in the cytoplasm, where they function as molecular sponges for specific microRNAs. Their regulatory functions are mediated through transcriptional, post-transcriptional, translational, and epigenetic mechanisms. Increasing evidence indicates that lincRNAs contribute to various aspects of Gastric Cancer (GC) pathogenesis, including disease initiation, metastasis, and recurrence. Consequently, they may serve as innovative biomarkers for diagnosis, prognosis, and therapeutic targeting. This article presents the first comprehensive study focusing on specific examples of GC-related lincRNAs. It reviews studies describing altered lincRNAs and examines the resulting disruptions in cellular pathways and dysregulated proteins with significant biological functions. Understanding the mechanisms underlying the abnormal expression of lincRNAs and their downstream effects in tumors is essential for advancing our knowledge of these molecules. Such insights could facilitate the identification of novel tumor markers that improve clinical diagnosis and prognostic evaluation of cancer.
Nanoceria as an Innovative Therapy for Endometriosis: Impact on Lesion Reduction and Therapeutic Optimization.
Fonseca LS, Gomes-da-Silva NC, Soares MAG … +7 more , Faria de Souza JI, Alencar LMR, Ricci-Junior E, Cavalcanti ADS, Machado DE, Perini JA, Santos-Oliveira R
Curr Med Chem · 2026 Mar · PMID 41941164 · Publisher ↗
INTRODUCTION/OBJECTIVE: Endometriosis is a chronic inflammatory disease with limited therapeutic options and frequent adverse effects. This study aimed to develop and evaluate cerium oxide nanoparticles (nanoceria) as a...
INTRODUCTION/OBJECTIVE: Endometriosis is a chronic inflammatory disease with limited therapeutic options and frequent adverse effects. This study aimed to develop and evaluate cerium oxide nanoparticles (nanoceria) as a potential therapeutic strategy for endometriosis, investigating their physicochemical characteristics, biodistribution, radiopharmacokinetics, safety profile, and therapeutic effects in an experimental animal model. METHODS: Nanoceria were synthesized using a previously established protocol and characterized by atomic force microscopy (AFM) and in vitro release assays. Female Wistar rats were used for in vivo experiments, including a surgically induced endometriosis model. Nanoceria were radiolabeled with technetium-99m to assess labeling stability, biodistribution, and pharmacokinetics following intraperitoneal administration. Therapeutic efficacy was evaluated through macroscopic and histological analysis of endometriotic lesions. Systemic safety was assessed using plasma biochemical markers. All analyses were conducted in an exploratory pilot design (n = 3 per group). RESULTS: AFM analysis revealed nanoceria with a mean diameter of 77.8 nm. The release profile showed a peak concentration at approximately 2 hours and a moderate elimination half-life (~4 hours). Radiolabeling efficiency remained above 98% for 24 hours. Biodistribution studies demonstrated predominant renal elimination and notable accumulation at endometriotic lesion sites. Pharmacokinetic analysis indicated rapid tissue distribution and low intravascular retention (t½ = 3.95 ± 1.09 h). Therapeutic evaluation showed a marked reduction in lesion size and inflammatory infiltrate in nanoceria-treated animals compared to those receiving the free cerium compound. Biochemical analyses indicated lower hepatic and metabolic alterations in the nanoceria groups, suggesting improved systemic safety. DISCUSSION: The findings indicate that nanoceria exhibit favorable physicochemical and biological properties, including stable radiolabeling, efficient tissue distribution, and selective accumulation in endometriotic lesions. The enhanced therapeutic response and reduced systemic toxicity compared to free cerium suggest that nanoscale formulation improves bioavailability and therapeutic performance. These results support the potential of nanoceria as a nanotechnology-based approach for endometriosis management. CONCLUSION: Nanoceria demonstrated effective lesion regression, targeted biodistribution, and a favorable safety profile in an experimental endometriosis model. Although exploratory, these results highlight nanoceria as a promising therapeutic candidate and provide a strong rationale for further confirmatory studies with expanded sample sizes and mechanistic evaluation.
Repurposing Diclofenac as an Anticancer Agent: Suppression of Breast Cancer and Progression through EPAS1-EFNA1 Regulation.
Zhang W, Huang Q, Zheng L … +4 more , Liao W, Zhao B, Liu B, Niu Z
Curr Med Chem · 2026 Mar · PMID 41941163 · Publisher ↗
INTRODUCTION: Breast cancer, the most common female malignant tumor, endangers women's health. Traditional anticancer drugs often lead to resistance, so new therapeutics are urgently needed. This study explored the anti-...
INTRODUCTION: Breast cancer, the most common female malignant tumor, endangers women's health. Traditional anticancer drugs often lead to resistance, so new therapeutics are urgently needed. This study explored the anti-tumor mechanism of diclofenac in breast cancer. METHODS: Diclofenac's effects on breast cancer cell proliferation, migration, invasion, and apoptosis were assessed via in vitro (MTT, Colony formation, Transwell, Wound healing, Flow cytometry, Immunofluorescence) and in vivo (Xenograft model) assays. RNA-seq identified diclofenac's target. EFNA1 expression was analyzed by RNA-seq, qRT-PCR, and Western blot. The luciferase assay investigated diclofenac-mediated EFNA1 transcriptional regulation; overexpression strategies validated EFNA1's involvement in mediating diclofenac's anticancer activities. RESULTS: Diclofenac inhibited proliferation, migration, and invasion, and induced apoptosis in T47D and MDA-MB-231 cells, and suppressed xenograft growth. It reduced EFNA1 expression by impairing EPAS1 binding to the EFNA1 promoter's -1353~-782 region; EFNA1 overexpression abrogated diclofenac's anti-tumor effects, confirming EFNA1 as a critical mediator of diclofenac's effects. DISCUSSION: Our findings reveal that diclofenac exerts anti-breast cancer effects by targeting EFNA1 via EPAS1-mediated transcriptional regulation. It not only provides novel insights into the COX-independent anticancer mechanism of diclofenac but also highlights EFNA1 as a potential therapeutic target for breast cancer, although further in vivo validation and larger-cohort studies are warranted. CONCLUSION: Diclofenac inhibits breast cancer progression by down-regulating EFNA1 through impairing EPAS1 binding to its promoter. These findings support repurposing diclofenac into an established and readily accessible medication as a promising and cost-effective agent for breast cancer treatment, while also underscoring EFNA1's potential role in guiding treatment stratification.
Genetic and Molecular Mechanisms Linking Breast Cancer to Meningioma Risk: Roles of EXO1, BRCA2, and ESR1.
Lin C, Hu J, Cai F … +3 more , Chen J, Huang J, Lin Y
Curr Med Chem · 2026 Mar · PMID 41941162 · Publisher ↗
BACKGROUND: Epidemiological evidence suggests increased meningioma risk in breast cancer patients, but causal relationships and underlying mechanisms remain unclear. METHODS: We performed two-sample Mendelian Randomizati...
BACKGROUND: Epidemiological evidence suggests increased meningioma risk in breast cancer patients, but causal relationships and underlying mechanisms remain unclear. METHODS: We performed two-sample Mendelian Randomization (MR) using 119 genome-wide significant SNPs to assess the causal effect of breast cancer on meningioma risk. Weighted Gene Co-Expression Network Analysis (WGCNA) identified shared gene modules, intersected with MR-nearby genes to pinpoint hub genes. Functional validation was conducted via in vitro assays in breast cancer (MCF7, MDA-MB-231) and meningioma (CH157-MN) cell lines. Candidate drug prediction was performed using Enrichr. RESULTS: MR analysis demonstrated a significant causal effect of breast cancer on meningioma risk (OR=1.22, 95% CI:1.09-1.37, p<0.01) without evidence of pleiotropy or reverse causation. WGCNA identified the MEblue module as highly correlated with both cancers; intersection with MR genes revealed EXO1, BRCA2, and ESR1 as key hub genes. These genes were upregulated in tumors, showing robust diagnostic performance (AUC>0.71). Knockdown experiments increased DNA damage and apoptosis, while ESR1 knockdown inhibited proliferation and invasion. Co-culture assays upregulated hub genes and inflammatory cytokines (IL-6, TNF-α). Azacitidine significantly downregulated these genes in MCF7 cells. DISCUSSION: Our integrative approach confirms breast cancer as a potential causal risk factor for meningioma mediated by EXO1-, BRCA2-, and ESR1-driven DNA repair and estrogen signaling pathways. Functional assays highlight their roles in tumor progression and microenvironmental inflammation via NF-κB signaling. Clinically, these genes may serve as biomarkers for early meningioma screening and as therapeutic targets. Azacitidine emerges as a promising candidate for precision intervention. Limitations include phenotype heterogeneity and lack of in vivo validation, warranting further study. CONCLUSION: This study provides genetic and functional evidence linking breast cancer to meningioma risk through DNA repair and hormonal pathways, supporting early risk assessment and targeted therapies to improve patient outcomes.
A Study of the Causal Association Between Autoimmune Diseases and Blinding Eye Diseases.
Yuan R, Zhang Y, Liu Z … +2 more , Xu P, Li K
Curr Med Chem · 2026 Mar · PMID 41941161 · Publisher ↗
INTRODUCTION: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and a...
INTRODUCTION: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) with cataracts, age-related macular degeneration (AMD), and glaucoma using Mendelian randomization (MR). METHODS: Genome-wide association study (GWAS) data were utilized to identify single- nucleotide polymorphisms (SNPs) strongly associated with AS, SLE, RA, cataracts, AMD, and glaucoma, which served as instrumental variables (IVs). The basic analysis was performed via inverse variance weighting (IVW), complemented by weighted median (WM), MR-Egger regression, weighted mode, simple mode, and MR-Robust Adjusted contour scoring technique (RAPS). The Cochran Q test, MR-Egger intercept test, MR-Steiger test, leave-one-out analysis, funnel plot, and MR-PRESSO model were used to assess the robustness of doing sensitivity analysis. RESULT: IVW estimated that primary angle-closure glaucoma (PACG) (OR=1.265), AMD (OR=1.063), DRY-AMD (OR=1.088), and cataracts were significantly related to RA. SLE is associated with drug-induced cataract (OR=1.113) and senile cataract (OR=1.012). AS is being linked with glaucoma (OR=1.265), PACG (OR=2.436), and primary open-angle glaucoma (POAG) (OR=1.400). DISCUSSION: RA, SLE, and AS can directly contribute to the development of cataracts, AMD, and glaucoma. These results endorse the interdisciplinary interventions approach that can incorporate rheumatology and ophthalmology. All investigations were restricted to individuals of European descent. These findings should be verified and expanded by performing multi-ethnic studies. CONCLUSION: The study is generally reliable in establishing the causal relationship between AS, SLE, RA, and selective blinding eye illnesses, with the rationale of applying clinical screening techniques and specific intervention strategies.
Chalcogen-modified Nucleic Acid Analogues.
Kulik K, Nawrot B
Curr Med Chem · 2026 Apr · PMID 41935367 · Publisher ↗
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