Mini reviews in medicinal chemistry最新文献

Sleep disorders and the resultant sleep deprivation (SD) are very common nowadays, resulting in depressed mood, poor memory and concentration, and various important changes in health, performance and safety. They may provoke further impairment of the cell lining of the blood vessels, as acting as a risk factor for cardiovascular disease (CVD) onset and progression. SD may lead to low neuronal regaining and plasticity, drastically affecting brain function. Thus, SD is a known risk factor for mental, behavioral and developmental disorders. Due to the inflammatory and oxidative stressful nature of SD, immune response modulation and antioxidants could be another therapeutic approach, apart from the already known symptomatic treatment with sedatives. Additionally, many drugs approved for other indications and under investigation, have been revisited due to their wide array of pharmacological activities. This review summarizes the main aspects of SD pathology and SD interrelated comorbidities and presents direct and indirect antioxidant molecules and drugs with multi-targeting potential that could assist in the prevention or management of these factors. A number of research groups have investigated well-known antioxidant compounds with multi-targeting cores, combining structural characteristics with properties including antiinflammatory, metal chelatory, gene transcription and immune modulatory that may add towards the effective SD and its associated comorbidities treatment.

O-GlcNAcylation is a non-canonical form of protein glycosylation that occurs in nuclear, cytoplasmic, and mitochondrial proteins among all multicellular eukaryotes. There are only two enzymes that regulate this post-translational modification, one of which is O-GlcNAcase, a glycoside hydrolase that catalyzes the hydrolytic cleavage of O-GlcNAc from protein substrates. Related studies have shown that the reduction of O-GlcNAc levels is closely related to Alzheimer's disease, which is maintained by reducing the aggregation of tau via inhibiting O-GlcNAcase. Various smallmolecule O-GlcNAcase inhibitors with different chemical structures have been developed and used as chemical probes to explore the O-GlcNAc pathway. Although many reported inhibitors have shown that O-GlcNAcase activity has single-digit nmol IC50 values in binding assays, and molecules, such as LY-3372689, have entered phase II clinical studies, further exploration of novel OGlcNAcase inhibitors with higher inhibitory activity and specificity is still worthy of attention. This article reviews the pathogenesis and therapeutic role of O-GlcNAcase in Alzheimer's disease, as well as the recent progress of O-GlcNAcase small molecule inhibitors, including sugar-derived or non-sugar scaffolds, and summarizes the clinical progress and potential prospects of O-GlcNAcase inhibitors.

Inflammation is a fundamental biological reaction to harmful stimuli, which is crucial in the initiation and advancement of different diseases, including rheumatoid arthritis, cardiovascular conditions, neurological disorders such as Alzheimer's and Parkinson's, and multiple cancer types. Chronic inflammation, in particular, contributes to irreversible tissue damage and the progression of disease. Thus, the suppression of key inflammatory mediators has become a promising therapeutic approach. Thromboxane A₂ (TxA₂), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) are among the mediators that have been thoroughly investigated for their roles in regulating immune responses and sustaining inflammation; therefore, targeting these mediators offers substantial therapeutic potential. In recent years, significant attention has been focused on heterocyclic compounds, especially pyridazine and pyridazinone derivatives, owing to their structural diversity and extensive biological activity. These scaffolds have shown significant effectiveness in regulating inflammatory pathways by limiting TxA₂ production, reducing TNF-α release, and disrupting IL-6 signaling. This review presents a comprehensive overview of pyridazine and pyridazinone-based compounds as potential anti-inflammatory agents. It highlights both traditional and current synthetic strategies used in their development and explores their mechanisms of action with respect to key inflammatory targets. Additionally, the study examines recent pharmacological assessments and preclinical results, offering insights into the medicinal uses of these substances. A brief perspective on future research directions is also included, emphasizing the need for further structural optimization, in vivo validation, and clinical translation. Collectively, these results highlight the potential of pyridazine and pyridazinone derivatives in the development of advanced anti-inflammatory pharmaceuticals.

The growing prevalence of multidrug resistance and its detrimental effects pose a significant threat to public health, which is one reason for the current interest in the introduction of novel agents. To combat this adverse effect and drug resistance, numerous drugs have been developed over time, and their safety is still being evaluated; derivatives or medications based on the carbazole moiety are one of the key contributors. Therefore, this review explores carbazole-based derivatives as possible drugs to treat Alzheimer's, diabetes, inflammation, cancer, and many more, along with their synthetic schemes, SARs, and activity. Some of the carbazole-based drugs available in the market and under clinical trials are also tabulated. By integrating this insight, describe how these compounds are being reinvented as targeted therapeutic agents. This comprehensive analysis is designed to guide researchers in developing next-generation drugs to address various challenges and leverage the unique pharmacological properties of carbazole-derived drugs.

Medical diagnostics, environmental monitoring, and food safety are key domains being transformed by the ongoing revolution in optical biosensors. These light sensors are highly sensitive and specific for detecting specific biological interactions, allowing for real-time, label-free detection. Biorecognition elements (such as enzymes, antibodies, or nucleic acids), following interaction with the target analyte, generate optical signals based on the same key principles as optical biosensors. Surface plasmon resonance (SPR), fluorescence-based sensors, and fiber optic sensors offer a wide range of biosensors capable of detecting a broad spectrum of biological and chemical agents at trace concentrations. Diagnostic capability has become efficient and rapid with advances in nanotechnology and microelectronics, particularly in nanopores. Monitoring of cardiovascular health using wearable optical biosensors, such as photoplethysmography (PPG), is a non-invasive method. It has also been recently improved to better track heart rate and blood pressure, as well as evaluate mental and vascular health. Wearable optical biosensors support technologies, such as continuous monitoring and early detection of anomalies, which help in personalized healthcare. Optical biosensors are particularly suitable for detecting pathogens, biomarkers, and pollutants in clinical settings, as well as for environmental monitoring and food safety assessments. These applications range from biopharmaceuticals to biotechnology and personalized care, which are used to monitor diseases, discover drugs, and detect pathogens. Despite progress, matrix interference with the sample matrix, sensor stability, and miniaturization remain challenges to be overcome. However, with future progress in materials science, nanotechnology, and increased integration with the Internet of Things (IoT), the potential for optical biosensors will continue to rise as portable, cost-effective, real-time data-analyzing diagnostic tools that expand accessibility to those in underserved regions. Developed using optical and electrochemical approaches, the biosensors reviewed in this article are discussed in terms of their principles, types, applications, and prospects, including their roles in healthcare and environmental sectors.

Musculin antisense RNA 1 (MSC-AS1) is a long non-coding RNA (lncRNA) located on human chromosome 8q13.3-q21.11. Emerging evidence shows that MSC-AS1 is either upregulated or downregulated in 16 types of human cancers, and is associated with clinical pathological features and patient prognosis in 12 of these cancers. It is widely believed that the dysregulation of MSCAS1 contributes to tumor cell growth, metastasis, epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming, and drug resistance formation. Mechanistically, MSC-AS1 can act as a competing endogenous RNA (ceRNA) by sponging 14 miRNAs to affect the expression of downstream mRNAs, or it may directly interact with proteins, both of which contribute to the activation of the PI3K/AKT and Wnt/β-catenin signaling pathways. Our review study suggests that MSC-AS1 is a potential cancer biomarker and therapeutic target. In summary, we have explained the research on MSC-AS1 related to cancer treatment, its expression patterns, functional characteristics, and molecular mechanisms in malignant tumors. We have further emphasized its significance in clinical prognosis and therapeutic applications.

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis and Crohn's disease, accounts for chronic inflammation in the entire gastrointestinal tract. Conventional treatments, such as amino salicylates, corticosteroids, immunomodulators, and biologics, can all alleviate symptoms; however, they may cause unwanted side effects and are extremely expensive. Most of the time, long-term treatment is also less effective. This review aims to discuss natural products (NPs) with therapeutic potential for IBD, emphasizing flavonoids, terpenoids, polysaccharides, and alkaloids. The compounds have been chosen based on literature reporting antiinflammatory, antioxidative, and immunomodulatory activities that relate to IBD pathophysiology. Preclinical evidence using in vivo and in vitro models and available clinical data provides the basis for the main pharmacological effects, mechanisms of action, and safety profiles of these NPs. The key molecular pathways that are targeted include the NF-κB, MAPK, and JAK/STAT signaling pathways, as well as the establishment of the gut microbiota and intestinal barrier functions. Standardization, bioavailability, and maximal dosing remain challenging issues even when experimental models show promising results for various NPs. Hence, this review stresses the urgency for well-designed clinical trials and suitable formulation approaches to translate these observations into efficacious and evidence-based therapies. Being a natural remedy option, NPs could be considered complementary or alternative treatments for IBD, demanding further interrogation within an integrated therapeutic paradigm.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally; however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence. Beta-2 adrenergic receptors (β₂-ARs) play a significant role in both the aetiology and management of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and potential synergistic effects with other medications. They are well-tolerated and effective in improving the quality of life and reducing exacerbations, making them an essential component of COPD treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD. This article provides an extensive overview of natural β₂ agonists. The current study emphasizes the rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4- benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5- (2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular docking studies. This paper also highlights numerous structure-activity relationship investigations and various novel β₂ agonists currently in clinical trials and patents. The present review will significantly aid in fostering the research of COPD.

Magnetic liposomes (MLs) are hybrid nanovesicles that combine the biocompatibility of lipid bilayers with the remote controllability of superparamagnetic nanoparticles. To the best of our knowledge, no prior review has systematically covered the literature on MLs published between 2020 and 2024, with a special focus on continuous-flow microfluidic synthesis. Here, we consolidate and critically assess recent advances in MLs' structural design, highlight remaining challenges, and propose future directions for clinical translation. MLs, as one of the types of biomimetic magnetic nanovesicles, are considered promising nanocarriers for biomedical applications. These applications include active drug targeting to specific tissues, magnetic resonance imaging, magnetic hyperthermia, controlled release, and other applications. This review aims to comprehensively classify current knowledge on the main structural types of MLs and their traditional (batch) and modern (continuous-flow) synthesis methods. The current advantages and potential challenges of microfluidics- based MLs synthesis are described. Detailed information on the variants of microfluidicsbased techniques is provided, along with examples and potential biomedical applications. For the main aspects of MLs synthesis and applications, schematic illustrations are provided. Finally, an outlook on the perspectives of further MLs development and applications is presented.

Breast cancer remains the most prevalent cancer among women worldwide, with increasing toxicity and resistance to current therapies posing a serious challenge to healthcare systems. The urgent demand for more effective and safer treatments has highlighted coumarin, a naturally occurring compound with a unique ring structure, due to its promising potential in combating breast cancer. Over the past three decades, numerous synthetic coumarin derivatives have been developed to enhance therapeutic efficacy. This review provides a comprehensive analysis of 18 reported coumarin- based compounds, focusing on their design strategies, mechanisms of action, and structureactivity relationships (SAR). Molecular docking studies targeting key enzymes, including tyrosine kinases, topoisomerases, and serine/threonine kinases, were examined to evaluate binding affinities and interaction patterns. Substitutions at the 3- and 6-positions of the coumarin scaffold were found to impact target binding significantly. Critical interactions, including hydrogen bonding, van der Waals forces, and hydrophobic contacts, were correlated with experimental anticancer activities, offering valuable insights into ligand-protein complex stabilization. Overall, the analysis underscores the potential of coumarin derivatives as promising leads for the rational design of novel anticancer agents with improved efficacy and selectivity.