Mini reviews in medicinal chemistry最新文献

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.

The urinary tract (UT) was once considered sterile, but now it is known to host a diverse community of microorganisms, known as the urinary microbiome. The collective microbiota is made up of bacteria, fungi, and viruses, necessary for maintaining UT health. This review aims to synthesize current knowledge on the urinary microbiome and clarify its emerging role as a key modulator in both health and a wide spectrum of UT disorders. Dysbiosis within this microbial community has been linked to conditions such as urinary tract infections (UTIs), interstitial cystitis/ bladder pain syndrome (IC/BPS), urinary incontinence, urolithiasis, benign prostatic hyperplasia (BPH), and even urinary tract malignancies. Advances in methodologies, such as expanded quantitative urine culture and metagenomics, have provided valuable insights into microbial variability influenced by factors like age, sex, and disease conditions. Additionally, this review explores the therapeutic potential of probiotics and bacteriophages, as well as the association of urinary microbiota with autoimmune and inflammatory conditions. Special emphasis is placed on translational relevance, including emerging microbiome-targeted therapies and personalized interventions for UTIs. Ethical considerations allied with UT microbiome research, such as data privacy, informed consent, and equitable access to emerging therapies, are also discussed. Despite substantial progress, challenges such as methodological heterogeneity, a lack of longitudinal data, and unresolved causal relationships persist. The study concludes by identifying key knowledge gaps and proposing future directions for multidisciplinary research to advance therapeutic innovation in urological health.

Artificial Intelligence (AI) is emerging as a valuable tool in pharmaceutical formulations, including the development of effervescent tablets (ETs). This review highlights how AI techniques are being explored to support ET formulation designs, optimize component ratios, predict disintegration and dissolution behavior, and control reactions through artificial neural networks, support vector machines, and machine learning. These techniques have been applied in recent studies to enhance stability, improve disintegration times, and flavor masking. Computational fluid dynamics simulations of effervescence and dissolution are underexplored for ETs. Data-driven approaches, like response surface modeling, require ingredient concentrations, tablet properties, consumer preferences, and predictive analytics for optimization. However, limited comprehensive datasets, complex reactions, environmental sensitivities, and ethical/regulatory considerations pose challenges. Overcoming these obstacles, as identified in the current literature, could enable AI to innovate ET development and personalization.

Quinoline is a biologically important bicyclic scaffold found in many natural products and medicinally relevant molecules. Quinoline-containing compounds continue to feature prominently in recent literature on hit identification and hit-to-lead campaigns targeting various biological pathways, underscoring the need for a review of the latest progress. This review presents recently reported quinoline-containing natural products, various synthetic methods for producing quinoline derivatives, and an overview of their diverse biological activities. The biological properties covered include anticancer, anti-inflammatory, antioxidant, anti-tubercular, α-glucosidase inhibitory, antimicrobial, anti-Alzheimer's, and antimalarial effects. Finally, a selection of representative quinolinebased chemical probes is presented to assist researchers in strategically designing novel quinoline derivatives for diverse biological applications.

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.

Recent trends have shown the development of various medicinally important compounds that specifically target B-cell receptor (BCR) pathways at various segments that have a major role in Bruton's tyrosine kinase (BTK) receptor, which belongs to the family of kinases. These kinases are usually situated close to the cell membrane due to which they participate in upstream processing of BCR signalling. Various molecules have been potentialized to target these signalling pathways of these kinase receptors in order to achieve a pharmacological effect. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of multiple diseases. BTK inhibitors work by regulating B-cell receptor signalling along with inflammatory pathways and immune cell interactions, offering more advanced treatment options compared to traditional therapies. In addition to BTK inhibitors, an extensive knowledge of the pharmacological mechanisms underlying the blockage of these receptors is necessary in order to more accurately forecast when and where a patient could need combination therapy or just one medication. Efforts have been made to facilitate translational discoveries, drug re-purposing concepts, and further development of precision medicine products. This thorough literature study has focused on studies published until June 2025.

Introduction: Breast cancer is a widespread and life-threatening disease. While FDAapproved anti-BC drugs have improved survival rates, issues like drug resistance and adverse effects highlight the need for new therapeutic options. Molecular hybridization, a modern drug discovery strategy, combines different pharmacophores or frameworks into a single molecule to enhance pharmacological activity and improve treatment outcomes. Hybridizing two or more heterocyclic moieties has become a promising approach in anti-cancer drug discovery.

Methods: This article reviews the role of heterocyclic hybrids in BC therapy, based on literature from 1995 to 2024 available in PubMed. Key heterocyclic hybrids, pyrimidine, triazole, indole, coumarin, beta-carboline, azepine, isoquinoline, benzoxepine, and platinum-core hybrids were included.

Results: Triazole, in particular, was found to be a highly effective scaffold for BC treatment when combined with indole, pyridazinone, and steroid pharmacophores.

Discussion: The article discusses novel molecular hybridization strategies, current BC treatment options, clinical studies, key functional groups, anti-apoptotic mechanisms, and protein-ligand interactions. Structure-activity relationships are explored to highlight desirable pharmacophoric features, aiding in the development of more effective BC therapies.

Conclusion: Each heterocyclic hybrid class of BC comprises some salient features and potentials, which may be further investigated to obtain novel effective heterocyclic hybrid molecules in BC therapy.

Inflammation is a key contributor to the pathophysiology of various chronic diseases, including cancer, arthritis, cardiovascular disorders, chronic wounds, and gastrointestinal conditions, many of which rank among the leading causes of mortality worldwide, according to the WHO. The prevalence of chronic inflammation-related diseases is projected to rise steadily over the next 30 years, with an estimated three out of five individuals dying daily as a result of such conditions. Consequently, there is a growing demand for the discovery of novel anti-inflammatory agents. Cyclooxygenases play a pivotal role in inflammatory processes, being responsible for the synthesis of prostaglandins. COX-1 is constitutively expressed and primarily associated with "housekeeping" physiological functions, whereas COX-2 is an inducible isoform involved in inflammatory responses. Due to its role in inflammation and relatively favorable gastric safety profile compared to traditional NSAIDs, COX-2 has emerged as a significant therapeutic target for inflammation-related disorders. However, the increased risk of stroke and heart attack associated with COX-2 inhibitors has led to the withdrawal of several approved COX-2-targeting drugs from the market. Consequently, the development of new COX-2 inhibitors with potent efficacy and minimal cardiovascular side effects is of critical importance. This review explores a range of oxygen- and nitrogen-containing heterocycles as potential anti-inflammatory agents, emphasizing their COX-2 inhibitory activity, structure-activity relationships, and interactions within the COX-2 active site, as reported in recent studies. The article covers research findings published from 2019 through the first quarter of 2025.

In the management of solid tumors, ionizing radiation is a critical therapeutic modality, particularly when surgical intervention is impractical due to patient-related factors, such as compromised health or elevated mortality risk. However, its non-selective action can cause serious side effects that negate the therapeutic benefits. Efforts have thus been made to identify pharmacological agents that can selectively protect normal tissues from exposure to ionizing radiation. Seven decades of study, however, have shown that the desired success has not been achieved in obtaining an ideal radioprotective agent. Moreover, even at optimal doses, the FDA-approved drug, amifostine (also known as WR-2721 [S-2- (3-aminopropyl-amino) ethyl phosphorothioic acid], exhibits significant toxicity. An ideal radioprotective agent can also be beneficial in environments where individuals are exposed to prolonged, low-dose radiation. Considering this, there is a pressing need to develop methods of shielding cells and patients from the deleterious effects of radiation, and a non-toxic radioprotective drug can be useful in both clinical and occupational contexts. Studies have shown that the fruits of Emblica officinalis and its cardinal phytochemicals, such as gallic acid, ellagic acid, quercetin, geraniin, corilagin, and kaempferol, have been demonstrated to mitigate radiationinduced side effects. Research has also demonstrated that fruits can reduce the severity of radiationinduced mucositis in head and neck cancer patients undergoing curative treatment. Currently, there are no clinically effective non-toxic medications that are beneficial in mitigating radiation-induced ill effects. In lieu of this, for the first time, this review compiles the positive effects of fruits, phytochemicals, and their byproducts, chyawanprash and triphala, on radiation-induced damage, the mechanisms by which these effects occur, and the gaps that must be filled in order for future research to help people and the agricultural and nutraceutical industries.

Millions of people worldwide are affected by neurodegenerative disorders (NDs), which include a broad range of clinical ailments that affect the brain or peripheral nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, etc. Neuronal cell death in NDs is often linked to oxidative stress; thus, antioxidant treatment can combat oxidative cell damage, and this strategy has been studied in neurodegenerative processes. Over the past 10 years, we have witnessed intense research activity on the biological potential of human monoamine oxidase (hMAO) inhibitors that have been associated with the prevention of oxidative stress and inflammation. These inhibitors have emerged as promising therapeutic agents, especially in the treatment of neurodegenerative diseases (NDs), where their core activity may help mitigate disease progression. An overview of the current state of numerous scaffolds, such as chromones, coumarins, chalcones, propargylamines, benzothiazoles, aminoisoquinolines, and the natural compounds, including ferulic acid, resveratrol, and chrysin, which combine antioxidant capability and hMAO inhibition is given in this review, with particular attention given to each scaffold's mechanism of action and structure-activity relationships (SARs), which are thoroughly discussed. Focusing on the dual mechanism of action, combining inhibition and antioxidant properties, as a potential therapy for neurodegenerative diseases, we have reviewed the different chemical classes of multi-targetdirected ligand (MTDL) inhibitors developed within this framework. Other central nervous system (CNS)-related enzymes, such as cholinesterases, carbonic anhydrases, and BACE-1, have also been explored as targets in the MTDL strategy. By understanding their biological activity, medicinal chemists can better comprehend biological activity and recommend more effective and specific ND treatments.