Current topics in medicinal chemistry最新文献

Introduction: Postoperative complications are common issues that may arise from anesthetic drugs or surgical procedures. This study aimed to investigate the protective and therapeutic effects of ginsenosides on anesthesia-associated side effects and postoperative complications.

Methods: This study was conducted following the PRISMA 2020 guidelines. A comprehensive search was conducted across PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library to identify relevant studies published prior to October 13, 2024. Predefined inclusion and exclusion criteria were applied, and duplicates were removed.

Results: Ginsenosides inhibit oxidative stress and enhance cognitive function by activating pathways such as phosphoinositide 3-kinase (PI3K)/Protein kinase B (PKB) (AKT)/glycogen synthase kinase-3 beta (GSK-3β), promoting neuroplasticity, alleviating oxidative stress, and modulating neuroinflammatory markers, as well as microglia and astrocytes. They help to maintain mitochondrial integrity, thereby reducing apoptosis and neurotoxicity caused by anesthetic agents. Ginsenosides also alleviate postoperative pain by modulating N-methyl-D-aspartate (NMDA) and suppressing inflammatory cytokines. They also improved neuropsychological problems by increasing Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). The anti-fatigue properties of ginsenosides are attributed to enhanced antioxidant activity, improved skeletal muscle metabolic function, and increased Adenosine Triphosphate (ATP) production.

Discussion: These results are consistent with prior studies demonstrating the neuroprotective effects of ginsenosides. Despite promising outcomes, the prevalence of animal studies and the absence of clinical data underscore the necessity for clinical validation and safety profiling in future research.

Conclusion: Preclinical evidence shows ginsenosides, particularly Rg1, Rb1, and Rg3, demonstrate promising protective and therapeutic effects against anesthesia-associated adverse effects and postoperative complications.

The employment of phytomolecules to treat cancer has become widespread in recent decades. Boswellic acids (BAs) are pentacyclic triterpenoids obtained from Boswellia oleo-gum resins. BAs are the primary active constituents of Boswellia resins and exhibit potent anticancer activity against numerous cancer cell lines. Consequently, they have garnered considerable attention as prominent anti-cancer agents. However, the pharmacokinetic characteristics of BAs, such as their low bioavailability and poor water solubility, pose significant barriers that limit their medicinal use. The aim of this review is to provide a thorough overview of the anticancer effects of BAs, along with their physiochemical parameters, pharmacokinetic profile, and structure-activity relationship (SAR). Furthermore, computational studies conducted on BAs to improve their therapeutic efficacy, relevant clinical studies evaluating BAs, the associated challenges, and future prospects have also been discussed. A systematic review of the literature was conducted to identify the effects of BAs in various cancers. The following databases were searched: PubMed, Web of Science, and Scopus, for prospective studies published between 2012 and 2025. Although BAs exhibit significant therapeutic potential, their clinical utility is limited by their pharmacokinetic profile. Focused studies on improved isolation techniques, the development of synthetic derivatives, and hybrid molecules are required to address these challenges. In addition, advancements in nanodrug delivery systems and computational studies are vital to overcome these barriers. Collectively, these strategies could prove helpful in establishing BAs as privileged scaffolds for developing anticancer drugs.

Breast cancer remains the second leading cause of cancer-related deaths worldwide, with mortality rates continuing to rise annually. While conventional treatments, such as surgery, chemotherapy, and radiotherapy, are available, they are not 100% effective and often damage healthy tissues, negatively impacting patients' quality of life. Naringenin, a promising phytonutrient, has demonstrated anti-cancer properties through various mechanisms that inactivate carcinogens. However, its therapeutic potential is limited by poor bioavailability and hydrophobic nature. Nanocarrier-based drug delivery systems, an application of nanotechnology, offer a promising solution to overcome these limitations. These systems enhance the solubility, circulatory half-life, and biodistribution of bioactive compounds like naringenin while reducing side effects. This innovative approach shows significant potential in improving breast cancer treatment outcomes.

Plant-powered nanotechnologies integrate the concepts of biological engineering and green synthesis to produce safe and environmentally friendly nanoparticles that address environmental and public health issues. Biological production, meanwhile, is a safe, biodegradable, as well as a sustainable method to create nanoparticles. Tabernaemontana divaricate, Calotropis gigantea (L.), Passiflora caerulea, Acorus calamus (rhizome), Cucurbita maxima (petals), Moringa oleifera (leaves), Piper nigrum, Ziziphus Spina Christi, Eucalyptus globulus, and Ziziphus oenoplia, etc., plants were among the medicinal flora used in the biological synthesis of Silver and Zinc oxide. Initially, phytochemical testing, scanning electron microscopy, energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction, and electron microscopy were employed to characterize the greensynthesized Zinc oxide and silver nanoparticles. These medicinal floras have proven tremendous potential in the development of nanoparticles for several purposes in medicine, cosmeceuticals, food science and technology, water treatment and purification, environmental cleanup, and agriculture. This review paper highlights the characteristics of biologically produced Zinc oxide and Silver Nanoparticles and investigates the broad spectrum of plants that can be utilized in a single-phase, rapid protocol preparation approach that prioritizes green principles over conventional ones. These biologically friendly silver and zinc oxide nanoparticles have the potential to be very useful in the field of biomedicine, agriculture, cosmetics, water treatment, food science and technology, and the energy sector. The biomedicinal applications of green synthesised nanoparticles are particularly intriguing, with potential in drug delivery, bioimaging, antibacterial treatments, anti-Leishmanial properties, and cancer therapy. Compared to previous approaches, these nanoparticles provide benefits in terms of controlled administration, less toxicity, and increased therapeutic effectiveness. Future studies must concentrate on the development of affordable, non-hazardous, ecologically safe, and self-degradable nanoparticles to aid in the commercialisation of nanotechnology in agriculture, food, healthcare, and energy.

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, which collectively increase the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD). Due to the growing global burden of MetS, there is increasing interest in nutraceuticals such as gamma-oryzanol (γ-ORY), a bioactive compound derived from rice bran oil (RBO), as potential therapeutic agents. A systematic literature search was conducted through July 2024 using PubMed, Google Scholar, and SciFinder. The keyword "gamma-oryzanol" was combined with terms related to MetS and its components. Original preclinical and clinical studies were included, while reviews and book chapters were excluded; however, their references were screened for additional relevant studies. Preclinical studies indicate that γ-ORY targets multiple molecular pathways, including activation of AMP-activated protein kinase, upregulation of peroxisome proliferatoractivated receptor-α, inhibition of nuclear factor-κB, and promotion of glucose transporter type 4 translocation. These mechanisms collectively improve glucose and lipid metabolism, enhance insulin sensitivity, and reduce inflammation. Clinical trials, primarily involving adults with T2DM, obesity, dyslipidemia, or postmenopausal women (aged 30-70 years, mixed ethnicities), report that γ-ORY reduces total cholesterol (10-15%), LDL-C (8-12%), triglycerides (10-18%), fasting glucose (10-25 mg/dL), and HbA1c (0.3-0.8%). Compared to conventional therapies such as statins (LDL-C reduction: 30-50%) or antihypertensives (e.g., irbesartan), γ-ORY demonstrates milder efficacy but better tolerability, and may enhance the antihypertensive effects of irbesartan. Notably, clinical studies consistently report a favorable safety profile for γ-ORY, with minimal adverse effects and no major safety concerns to date. Overall, γ-ORY shows promise as a safe, multitarget nutraceutical for MetS management, with antioxidant, anti-inflammatory, and lipid-lowering properties. However, the generalizability of current findings is limited by small sample sizes, inconsistent dosing regimens, and underrepresentation of diverse populations (e.g., various ethnic groups and pediatric cohorts). Large-scale, well-designed clinical trials are needed to validate its efficacy, optimize dosing, and assess long-term safety compared to standard therapies.

Introduction: Fungi are ubiquitous and play crucial ecological roles, but fungal infections pose serious threats to human, animal, and environmental health, with a significant economic and social burden. Current antifungal therapies face challenges, such as limited drugs, toxicity, and resistance, highlighting the urgent need for drugs with new mechanisms of action. The enzyme acetohydroxyacid synthase (AHAS) is a promising target, as it is involved in branched-chain amino acid biosynthesis, a pathway lacking in animals and already explored in herbicide development.

Methods: We conducted an integrative review covering the antifungal potential of known AHAS inhibitors and the development of novel inhibitors with antifungal activity within the PubMed, ScienceDirect, and Web of Science databases.

Results: A total of 590 articles were obtained, and after applying the inclusion and exclusion criteria, 17 articles were selected. The review identified commercial herbicides as potent AHAS inhibitors of plant and animal pathogenic fungi and to have a broad spectrum of antifungal activity against many species, such as Candida albicans, C. auris, Cryptococcus neoformans, Aspergillus fumigatus, and Saccharomyces cerevisiae.

Discussion: Based on these results, several compounds were designed, synthesized, and evaluated as antifungal agents, showing promising inhibitory properties against fungal AHAS and growth. Structural features of AHAS from different organisms were also investigated to guide drug development.

Conclusion: Considering structural insights and experimental data, AHAS inhibitors showed promising profile as broad-spectrum antifungals, with low toxicity to humans and the environment, supporting a One Health approach to control fungal infections across human, animal, and environmental health.

Introduction: Ovarian cancer (OC) is a heterogeneous cancer with a high death rate and poor prognosis. Identifying precise and reliable prognostic biomarkers is crucial for the treatment of OC.

Methods: Anoikis-related DEGs were screened from the differentially expressed genes (DEGs) between the OC group and the control group and then subjected to functional enrichment analysis. A protein-protein interaction (PPI) network was developed to obtain candidate genes. Then, LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) analysis were employed to select biomarkers, followed by conducting gene set enrichment analysis (GSEA). Correlations between the biomarkers and immune infiltration, drug sensitivity, and immunotherapy response were assessed by the Spearman method. The expression of the biomarkers in cells was measured by scRNA-seq analysis.

Results: We obtained 142 anoikis-related DEGs, which were mainly enriched in apoptosis-relevant pathways. A total of 16 candidate genes were acquired from the PPI network. Then, STAT3 and BCL2L1 were selected via LASSO regression and SVM-RFE analysis as two biomarkers for OC. BCL2L1 was closely associated with the infiltration of 5 immune cell types and 32 drugs, while STAT3 exhibited notable correlation with the infiltration of 6 immune cell types and 13 drugs. The Tumor Immune Dysfunction and Exclusion (TIDE) score was positively correlated with the two biomarkers. Moreover, STAT3 and BCL2L1 were expressed in most cells, with a high expression of STAT3 in endothelial cells.

Discussion: This study integrated bulk and single-cell transcriptomics to identify STAT3 and BCL2L1 as two anoikis-related biomarkers linked to the immune infiltration and drug sensitivity of OC, showing potential value for patient stratification and therapy. These findings suggested that targeting the STAT3/BCL-xL axis and combinational immunotherapy might be an effective strategy for OC treatment, which, however, should be further verified by functional and clinical experiments.

Conclusion: This study identified two anoikis-related biomarkers for OC, contributing to the clinical diagnosis of OC and its treatment.

Introduction: Evodiamine, a quinazoline alkaloid derived from the Evodia rutaecarpa plant, has gained significant attention owing to its promising anticancer properties. However, its clinical applications are hampered by inherent challenges, including low water solubility, poor bioavailability and potential toxicity. This study reviews the current status and the medicinal chemistry efforts to accelerate the pace of evodiamine clinical applications in cancer therapy.

Methods: A comprehensive literature search in four electronic databases (PubMed, Scopus, Web of Science, Google Scholar and ScienceDirect) for this study, only English language publications have been evaluated based on their titles, abstracts and full text using keywords like evodiamine, anticancer, evodiamine derivatives, nanoformulation.

Results: Structural modification and nano-delivery strategies significantly improve the pharmacokinetic profile of evodiamine, reduce toxicity, and enhance its therapeutic efficacy. These strategies provide better bioavailability, increased target specificity and improved anticancer potential.

Conclusion: Integrating structural modification with nanotechnology presents a promising approach to address the challenges associated with evodiamine. This combination can potentially maximize its therapeutic efficacy in cancer treatment, paving the way for its clinical translation.

Introduction: This research endeavors to thoroughly examine the expression patterns, clinical relevance, and possible regulatory networks of PHD finger protein 19 (PHF19) in pheochromocytoma and paraganglioma (PCPG). PHF19, known for its role in tumor biology, is being investigated as a potential prognostic biomarker and immunotherapy target in PCPG.

Methods: We examined RNAseq data from 184 PCPG tissues and 3 normal tissues sourced from The Cancer Genome Atlas (TCGA), as well as 84 PCPG tissues and 6 normal adrenal tissues from the GSE19422 dataset. Utilizing R software, we conducted differential expression analysis, Kaplan-Meier survival analysis, Cox regression, and gene set enrichment analysis (GSEA). Additionally, PHF19 expression in PCPG cell lines was confirmed by quantitative real-time PCR (qRT-PCR).

Results: In PCPG tumor tissues, the expression of PHF19 was markedly higher than that in normal tissues (mean expression: 4.014 ± 0.044 versus 2.886 ± 0.205, p = 0.001). ROC analysis yielded an AUC of 0.940 (95% CI: 0.881-0.999), indicating PHF19's potential as a diagnostic biomarker. Elevated PHF19 expression was significantly associated with worse overall survival (OS) (HR: 9.45; 95% CI: 1.11-80.09; p = 0.039). PHF19 expression was significantly associated with multiple biological pathways, including steroid hormone biosynthesis and immune-related processes. PHF19 expression positively correlated with central memory T cell (Tcm) and effector memory T cell (Tem) infiltration, while negatively correlating with B cell infiltration and immune checkpoint genes (e.g., CD274 and SIGLEC15). Additionally, PHF19 expression correlated with sensitivity to specific chemotherapeutic agents, including vinblastine and etoposide.

Discussion: The results imply that PHF19 could serve as a potential prognostic indicator and immunotherapy target in PCPG. Its association with immune cell infiltration and immune checkpoint genes suggests a multifaceted role in the tumor immune microenvironment. The correlation with drug sensitivity highlights the potential for PHF19 to influence treatment outcomes. These findings underscore the importance of further investigating PHF19 as a potential immunomodulatory node and biomarker in PCPG; however, functional validation is required before any therapeutic targeting can be advocated.

Conclusion: This study establishes PHF19 as a potential prognostic indicator and immunotherapy target in PCPG, highlighting its immunomodulatory potential and the need to validate its therapeutic value functionally. Subsequent studies should focus on corroborating these results in broader cohorts and on probing the therapeutic prospects of targeting PHF19 in PCPG.