Current topics in medicinal chemistry最新文献

{"title":"Integrative Analysis Reveals Genes Causal Relation with Ovarian Cancer and aging.","authors":"Lanhui Qin, Chongze Yang, Rui Song, Pei-Yin Chen, Zijian Jiang, Weihui Xu, Guanzhen Zeng, Jin-Yuan Liao, Liling Long","doi":"10.2174/0115680266358687250507041056","DOIUrl":"https://doi.org/10.2174/0115680266358687250507041056","url":null,"abstract":"<p><strong>Background: </strong>Exploring the correlation between ovarian cancer and aging has great significance for understanding the pathogenesis of ovarian cancer and formulating targeted therapeutic regimens.</p><p><strong>Objective: </strong>This computational study aims to identify and validate key genes in monocyte subtypes related to ovarian cancer and aging, exploring potential causal relationships.</p><p><strong>Method: </strong>We collected single-cell RNA sequencing data (GSE157007, GSE184880), GWAS data (14,049 samples and 40,941 controls from a European population), and eQTL data of ovarian cancer and aging. Using R software packages like Seurat and singleR, we conducted data integration, quality control, cell classification, and differential gene expression analysis to identify intersecting monocyte subtype genes in ovarian cancer and aging. We employed summary data-based Mendelian randomization (SMR) analysis and Heterogeneity in Dependent Instruments (HEIDI) tests to pinpoint causal genes. Further single-cell functional analyses (gene switching, cell communication, metabolic pathway analysis), Bulk RNA sequencing validation, functional enrichment, and protein- protein interaction (PPI) analyses elucidated these genes' biological roles.</p><p><strong>Results: </strong>The dataset included 123,280 cells, revealing differential gene expression in classical monocytes (104 genes), intermediate monocytes (43 genes), and myeloid dendritic cells (39 genes). SMR and HEIDI identified causal relationships for 7 genes in classical monocytes, 3 in intermediate monocytes, and 3 in myeloid dendritic cells with ovarian cancer. Bulk RNA seq validation confirmed six monocyte genes as causal in ovarian cancer and aging. TREM1, SERPINB2, and CD44 were upregulated, while DST was downregulated; SLC11A1 and PNRC1 showed contradictory patterns. Interactions with NK and T cells involved LGALS9 - CD44/45 receptors. Riboflavin metabolism was a common enriched pathway.</p><p><strong>Conclusion: </strong>This study identified six specific monocyte genes as potential therapeutic targets for ovarian cancer and aging.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Medicinal and Nutraceutical Frontiers of Tinospora Cordifolia in Stress and Cancer Management.","authors":"Akansha Jaiswal, Kulbhushan Thakur, Atika Chandra, Tejveer Singh, Bilal Ahmad Mir, Shailendra Goel, Rajesh Tandon, Vijay Rani Rajpal","doi":"10.2174/0115680266347636250505063601","DOIUrl":"https://doi.org/10.2174/0115680266347636250505063601","url":null,"abstract":"<p><p>Tinospora cordifolia, commonly known as Guduchi, Giloy, or Amrita, has been a cornerstone of traditional medicine for centuries and is renowned for its diverse nutraceutical and medicinal potential. The plant exhibits immunomodulatory, antioxidant, anti-inflammatory, and anti-viral activities due to its rich array of bioactive compounds, including alkaloids, diterpenoid lactones, polysaccharides, and others. These properties make Giloy a promising candidate for a variety of therapeutic applications. Further, as oxidative damage contributes to chronic diseases by affecting essential biomolecules, the antioxidant phytochemicals found in T. cordifolia counter the free radicals and offer significant health benefits. This comprehensive review delves into the health benefits and therapeutic efficacy of Giloy, with a particular focus on its mechanisms for mitigating stress and combating cancer. The preclinical and clinical studies have demonstrated Giloy's ability to enhance antioxidant defences and induce apoptosis in cancerous cells. Additionally, it has shown potential in adjunct therapy to improve the quality of life for cancer patients by reducing the side effects associated with conventional cancer therapies. By exploring the multifaceted potential of T. cordifolia in modern medicine, this review aims to bridge the gap between traditional knowledge and contemporary scientific insights by addressing the underutilization of ancient herbal remedies in evidence-based healthcare. It also discusses future research directions and probable applications of Giloy in clinical practice, highlighting the importance of this ancient remedy in the context of modern healthcare practices, especially in cancer and stress management.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Diphenylsilane Compounds as Potential Inhibitors of Zn-Metalloproteinase Thermolysin Using Artificial Neural Networks.","authors":"Yudith Cañizares-Carmenate, Facundo Perez Gimenez, Roberto Diaz-Amador, Francisco Torrens, Juan A Castillo-Garit","doi":"10.2174/0115680266369656250428053942","DOIUrl":"https://doi.org/10.2174/0115680266369656250428053942","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Artificial neural networks are very powerful machine learning and artificial intelligence tools for computer-aided drug discovery. This method offers advantages over traditional approaches related to saving time and money. The aim of this work is to develop machine-learning artificial neural networks for computer-aided discovery of potential thermolysin metalloprotease inhibitor drug candidates.</p><p><strong>Methods: </strong>In this work, MLP (Multilayer Perceptron) and RBF (Radial Basis Function) neural networks with a general 5:n:1 architecture are developed to find a non-linear correlation between five molecular descriptors obtained by genetic algorithm, and the inhibition of the enzyme thermolysin, expressed as pKi. The AD (applicability domain) of the model was determined using the AMBIT Discovery software, and the in silico activity profile of a series of diphenylsilanes obtained by chemical synthesis was evaluated.</p><p><strong>Results: </strong>The proposed models show a better fit than the linear model in both series (R2 MLR = 0.71 for the training set and R2 MLR = 0.72 for the prediction set). In the case of the MLP, R2 values close to 0.90 are found and all the compounds are inside the AD of the model. Although the RBF-type models show instability in training, networks with a performance greater than 0.80 are found. However, only the MLP-type models are taken into account to predict the activity of a series of 17 diphenylsilanes. Finally, three compounds are identified as the most promising thermolysin inhibitors.</p><p><strong>Conclusion: </strong>This methodology offers advantages over traditional methods related to saving time and money. Furthermore, the results obtained suggest that the three identified compounds could be used for the treatment of cardiovascular pathologies because of their homology with human vasopeptidases.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Breast Cancer Therapy: The Pivotal Role of Nanoparticles.","authors":"Lalit Kumar, Ritesh Rana, Isha Singh, Neelam Sharma, Vikas Aggarwal, Nisha Gupta, Vuluchala Jyothiraditya","doi":"10.2174/0115680266354524250424162638","DOIUrl":"https://doi.org/10.2174/0115680266354524250424162638","url":null,"abstract":"<p><strong>Introduction: </strong>Globally, breast cancer (BC) affects a greater number of women than any other kind of cancer, and it is the second leading cause of death after lung cancer. The current standard of care for cancer treatment is the surgical excision of the malignant tumor followed by adjuvant therapy with chemotherapy or radiation. Regrettably, the side effects of radiation and chemotherapy frequently cause harm to healthy tissues and organs, hence limiting the effectiveness of these treatments in addressing BC. Recently, various nanoparticles (NPs) have been discovered and manufactured with the capacity to selectively target cancerous cells while minimizing harm to normal cells or organs. As a result, the utilization of NPs-mediated targeted drug delivery systems (DDS) has emerged as a promising method for treating BC.</p><p><strong>Objective: </strong>The primary aim of this review was to provide a concise overview of the function of different nanoparticles in the specific delivery of anticancer medications to eradicate breast cancer.</p><p><strong>Methods: </strong>The present review paper performed a literature inspection using several search engines such as PubMed, Google Scholar, and Science Direct.</p><p><strong>Results: </strong>In addition to their ability to selectively target tumor cells and minimize side effects, nanoparticles (NPs) possess other distinctive characteristics that make them highly desirable for cancer treatment. These include low toxicity, excellent compatibility, ease of preparation, high photoluminescence for in vivo bioimaging, and the capacity to efficiently load drugs due to their adjustable surface functionalities.</p><p><strong>Conclusion: </strong>This study provides a comprehensive examination of recent therapeutic studies that utilize various nanoparticle-mediated drug delivery systems as alternatives to established therapy techniques for breast cancer. This study will elucidate the importance of nanoparticle-mediated drug delivery systems (DDS) and provide a roadmap for identifying the optimal approach for future targeted drug delivery, specifically for the treatment of breast cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization, Preparation, and Cytotoxic Potential of Pyrus communis Extract Loaded Ethosomes on Skin Cancer Cell Lines.","authors":"Kiran Kangra, Vandana Garg, Anju Dhiman, Rohit Dutt","doi":"10.2174/0115680266349097250418135927","DOIUrl":"https://doi.org/10.2174/0115680266349097250418135927","url":null,"abstract":"<p><strong>Background: </strong>Skin cancer is one of the most prevalent cancers globally and is considered a serious public health problem associated with high death rates. The current therapeutic regimes for skin cancer are limited by their low bioavailability, generation of resistance, or adverse side effects. Many fruit extract-based nutraceuticals hold potential as topical treatment methods. Pyrus communis (Pear) fruit extract is a rich source of cholinergic acid, presently used as therapy for various skin diseases. Thus, it qualifies as a promising candidate for skin cancer treatment.</p><p><strong>Objective: </strong>The objective of the study is to evaluate the cytotoxicity of Pyrus communis extract entrapped in ethosomes.</p><p><strong>Methods: </strong>In this study, Pyrus communis fruit extract was formulated in ethosomes using the hot method and optimized using central composite design. The optimized ethosomes were characterized in vitro for particle size distribution, zeta potential, entrapment efficiency, morphology, and particle stability.</p><p><strong>Results: </strong>Preliminary phytochemical screening results suggest that PCHE contains a significant amount of phenolic compounds compared to other extracts (PCEA and PCAE). The presence of these phenolic compounds contributes to the strong antioxidant and cytotoxic effects of PCHE, which are observed in a dose-dependent manner. Analysis through GC-MS has identified chlorogenic acid, arbutin, ursolic acid, quercetin, and epicatechin are present in PCHE. Based on the initial testing of the extracts, PCHE was chosen for the preparation of ethosomes. The optimized ethosomes were found to have a particle size of 699 nm and a zeta potential of -16.07. Transmission Electron Microscopy illustrated a closed, spherically symmetrical structure of the ethosomes. Additionally, the Franz diffusion cell analysis for percutaneous absorption using egg membrane indicated a steady-state flux of the drug from the ethosomes. The formulation's cytotoxicity potential was assessed using the epidermoid carcinoma cell line (A431) through the MTT assay. The results show that the ethosome formulations exhibit cytotoxic activity better than PCHE extract. 1 Conclusion: In sum, the result of this study clearly points out that Pyrus communis extract entrapped in ethosomes, prepared by hot method, displayed a cytotoxic potential against skin cancer cell lines. This ethosomal formulation can be harnessed for skin cancer therapy through further mechanistic analysis and animal studies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-aided Drug Design: Part I.","authors":"Igor José Dos Santos Nascimento","doi":"10.2174/0115680266409158250430065509","DOIUrl":"https://doi.org/10.2174/0115680266409158250430065509","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-aided Drug Design: Part II.","authors":"Igor José Dos Santos Nascimento","doi":"10.2174/0115680266409269250430060426","DOIUrl":"https://doi.org/10.2174/0115680266409269250430060426","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.","authors":"Seidu A Richard","doi":"10.2174/0115680266372339250418052436","DOIUrl":"https://doi.org/10.2174/0115680266372339250418052436","url":null,"abstract":"<p><p>Neonatal brain injury (NBI) encompasses a variety of neurological acquired conditions affecting newborns. These conditions include hypoxia-ischemia, hyperoxic, periventricular leukomalacia, intrauterine infection, as well as perinatal cerebral hemorrhage. Each year, thousands of babies are born with signs of brain injury. It is estimated that two-thirds of these newborn infants with brain injury would either die or survive with mild to severe neurologic sequelae, largely due to the absence of no widely accepted treatment methods. Erythropoietin (Epo) is a humoral intermediary associated with the maturation as well as the proliferation of erythroid progenitor cells. Systematic administration of Epo triggers the elevation of Epo levels in cerebrospinal fluid (CSF) extracts, which means that Epo is capable of crossing the blood-brain barrier into the CSF. It has been reported that Epo treatment enhances the brain's network connectivity, improving local information transmission and promoting a shift toward a more integrated and consistent network architecture. This, in turn, augments both local and global connectivity efficiency. Exogenous Epo was found to be capable of regulating neurogenesis. Moreover, Epo was also reported to be associated with the inhibition of demyelination of axons, as well as the production of myelin-derived inhibitory proteins, which are inhibitory factors involved in axonal extension. Administration of recombinant human erythropoietin in neonatal rats provided neuroprotection against hyperoxiainduced oxidative stress. Furthermore, Epo administration during the neonatal period was shown to reverse molecular alterations associated with impaired development of the potassium-chloride cotransporter isoform 2 (KCC2), as well as deficits related to preterm birth during the postnatal period. Moreover, Epo was capable of blocking microglial stimulation, decreasing phagocytosis in vitro, as well as inhibiting the generation of inflammatory cytokines in vitro as well as in vivo. Thus, Epo via EpoR is able to influence brain connectivity, synaptogenesis, neurite repair, oxygeninduced brain injury, potassium chloride co-transporters, and inflammation via key signaling pathways to induce therapeutic as well as neuroprotection in NBI. Thus, Epo is a very promising neuroprotective as well as a therapeutic agent in the treatment of NBI. This review aimed to explore the neuroprotective and therapeutic mechanisms of Epo in NBI, as well as the potential of Epo variants.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Synthetic Advancement and Medicinal Applications of Asymmetric Cyclic Pyrazoline-based Hydrazine Derivatives: A Review.","authors":"Dattatraya Raut, Raghunath Bhosale, Dnyandev Bhosale, Anjana Lawand, Mahesh Hublikar","doi":"10.2174/0115680266374814250422053723","DOIUrl":"https://doi.org/10.2174/0115680266374814250422053723","url":null,"abstract":"<p><p>Chemistry research focuses on reducing energy and minimizing harmful byproducts. Pyrazoline and its derivatives have various pharmacological properties. This study aims to compile procedures for creating pyrazoline scaffolds from academic articles and online resources, such as Scopus, Google Scholar, Web of Science, Science Direct, Research Gate and libraries, aiming to minimize environmental and human health impacts. The primary objective is to determine the structural modifications and chemical groups that enhance their bioactivity, low toxicity, and handling. Furthermore, the review explores the bioavailability, synthetic challenges, and progress made in utilising pyrazoline derivatives in pharmaceutical and synthetic organic chemistry. The only goal is to provide insight into the creation of pyrazoline hybrid molecules that are very effective and less hazardous.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing 1,4-Dihydropyridines-Based Multitarget Therapeutics: Recent Advances and Future Directions.","authors":"Aditi Soni, Monika Sharma, Rajesh K Singh","doi":"10.2174/0115680266375345250414050338","DOIUrl":"https://doi.org/10.2174/0115680266375345250414050338","url":null,"abstract":"<p><strong>Background: </strong>1,4-Dihydropyridines (1,4-DHPs) serve as versatile scaffolds in medicinal chemistry, exhibiting multitarget potential with anticancer, cardiovascular, antioxidant, antiinflammatory, antimicrobial, and analgesic effects. Structural modifications enhance their binding affinity, bioavailability, and selectivity.</p><p><strong>Aim: </strong>This review aims to explore the broad therapeutic potential of 1,4-DHPs by analyzing their biological activities and structure-activity relationships (SAR). Additionally, it seeks to provide medicinal chemists with insights into key structural modifications that can optimize their pharmacological efficacy.</p><p><strong>Method: </strong>A comprehensive literature search was conducted in PubMed, ScienceDirect, Elsevier, and Google Scholar, prioritizing peer-reviewed studies from the last decade. Inclusion criteria focused on pharmacological properties, SAR, and therapeutic potential of 1,4-DHPs, while nonpeer- reviewed or irrelevant studies were excluded. Data extraction analyzed SAR trends, emphasizing the impact of structural modifications on binding affinity, bioavailability, and biological activity.</p><p><strong>Results: </strong>The review highlights that specific modifications in aromatic substituents, ester groups, and heterocyclic rings play a crucial role in enhancing the biological activity and selectivity of 1,4- DHPs. Their ability to modulate key enzymes and receptors contributes to their effectiveness as multitarget agents. Comparative SAR analysis provides evidence of the potential of 1,4-DHPs as next-generation therapeutics.</p><p><strong>Conclusion: </strong>1,4-DHPs offer a promising framework for drug development, with the potential to address complex, multifactorial diseases. By understanding and optimizing SAR, medicinal chemists can design more selective and potent 1,4-DHP-based drugs. Future research should focus on refining these structural modifications to unlock their full therapeutic potential.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}