Current topics in medicinal chemistry最新文献

{"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, Dnyandev Bhosale, Raghunath Bhosale, Anjana Lawand, Mahesh Hublikar","doi":"10.2174/0115680266374814250422053723","DOIUrl":"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}

{"title":"Bioactive Compound Chemistry and Antiasthmatic Activity of Betulinic Acid and Taraxerol in Experimental Models.","authors":"Shiv Narayan, Gaurav Krishna, Raghav Mishra","doi":"10.2174/0115680266358488250421012523","DOIUrl":"10.2174/0115680266358488250421012523","url":null,"abstract":"<p><strong>Background: </strong>The natural molecules betulinic acid (BA) and taraxerol (T) have many biological and therapeutic uses, one of which is the relief from asthma symptoms. This study wasThis study aimed to assess BA and T effectiveness in treating bronchial asthma and perform a molecular docking study to find the binding energy of BA and T with β-adrenoceptor.</p><p><strong>Methods: </strong>Using ethanol as the solvent, the Bacopa monnieri leaves were extracted using a soxhlet equipment. As a reference medicine, budesenoid was utilised. With PyRx 0.8, the molecular docking experiment was conducted using AutoDock vina. The protocol followed by the acute toxicity study was the OECD guideline 425. The effectiveness of the test medication in alleviating asthma was determined using an anaphylactic microshock model in guinea pigs.</p><p><strong>Results: </strong>Molecular docking analysis showed high binding affinities of BA (-7.95 kcal/mol) and T (-8.23 kcal/mol) to LOX-5, which could suppress the synthesis of leukotriene, one of the central mediators of asthma pathogenesis. In vivo study, the BA and T treatment prolonged pre-convulsion time in guinea pigs up to 506.66 seconds as compared with the control (406.6 seconds, p < 0.05). This suggests protection against bronchial hyperresponsiveness. ELISA assays demonstrated that BA and T decreased the levels of TNF-α and increased IL-10, indicating a potential modulation of inflammation (p < 0.05). Markers of oxidative stress were lowered in treated animals, as demonstrated by the lowered MDA and enhanced activities of antioxidant enzymes such as SOD, CAT, and GSH, suggesting a protective effect against oxidative lung damage (p < 0.05). Histological analysis confirmed a decrease in inflammatory cell infiltration and airway remodeling in the treated groups compared to the OVA-induced controls.</p><p><strong>Conclusion: </strong>The results of the animal studies showed that BA and T reduced anaphylaxis, suggesting that it could be a viable alternative to current asthma treatments in the future. The results of the molecular docking investigation, however, showed that BA and T may indeed bind to the target receptor, opening the door to new treatment possibilities.</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":"143986131","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":"The Effects of Plasma Exosomes of Young Individuals Compared to Old Ones on Age-Related Inflammation and Lineage Differentiation of CD34+ Umbilical Cord Blood Hematopoietic Stem Cells.","authors":"Maryam Helali, Saeid Kaviani, Shaban Alizadeh, Reza Afrisham, Mohammad Ahmadvand","doi":"10.2174/0115680266361607250418052405","DOIUrl":"10.2174/0115680266361607250418052405","url":null,"abstract":"<p><strong>Introduction: </strong>Cellular aging is a complicated event known for gradually reducing homeostasis, leading to a higher susceptibility to diseases and mortality. Since the behavior of Hematopoietic Stem Cells (HSCs) is potentially affected by plasma-derived exosomes, this study aimed to investigate whether the plasma-derived exosome of young and elderly human donors can deliver \"youth\" or \"aging\" signals into human umbilical cord blood-derived HSCs in vitro.</p><p><strong>Methods: </strong>Exosomes were isolated from four young (Y-exo) and four old (O-exo) donors. Umbilical cord blood-derived HSCs were exposed to two concentrations of exosomes (5 and 10 μg/mL). Then, lineage differentiation (CD41 and CD38), the mRNA and protein expression of IL-1β and IL- 6, and NFκB activity were evaluated using flow cytometry, qRT-PCR Enzyme-Linked Immunosorbent Assay (ELISA) methods, and western blot techniques, respectively.</p><p><strong>Results: </strong>The lineage-specific markers CD41 and CD38 expression were increased after exposure to O-exo compared to Y-exo at the concentration of 10 μg/mL (P<0.001). The HSCs treated with 10 μg/mL O-exo increased protein and mRNA expression of IL-1β and IL-6 compared to Y-exo at 10 μg/mL concentration (P<0.01). Furthermore, a significant difference was seen in p-NF-κB levels between O-exo and Y-exo at the concentration of 10 μg/mL (P=0.0014).</p><p><strong>Conclusion: </strong>Our findings advocated the concept that circulating exosomes of old and young individuals may differently affect the pathways involved in the aging process in HSCs.Therefore, exosomes may be applied as therapeutic agents for regenerative medicine.</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":"143957235","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 Organoid Culture Systems in Pancreatic Cancer.","authors":"Lei Liu, Jing Sun, Sheng Chen, Xuechan Tang, Shuai Zhang, Min Wang, Qian Yue, Changqing Zhong, Lianyong Li","doi":"10.2174/0115680266392238250423115420","DOIUrl":"https://doi.org/10.2174/0115680266392238250423115420","url":null,"abstract":"<p><p>Despite advances in therapeutic regimens, Pancreatic Cancer (PC) still remains an aggressive malignancy characterized by high treatment resistance, mortality, and poor clinical outcome. Hence, there is an urgent need for more effective therapeutic methods to improve the survival of PC patients. Currently, organoid culture systems have emerged as a preclinical research model for studying cancer progression, biology, and treatment responses, bridging the translational gap between in vivo and in vitro models. This review summarized the common culture systems of PC organoids, paving the way for precision medicine in PC.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976921","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":"Artificial Intelligence-Driven Innovations in Pharmaceutical Development and Drug Delivery Systems.","authors":"Ting Zhu, Bing Liu, Ning Chen, Yuchen Liu, Zixuan Wang, Xue Tian","doi":"10.2174/0115680266373236250411060857","DOIUrl":"https://doi.org/10.2174/0115680266373236250411060857","url":null,"abstract":"<p><p>As Artificial Intelligence (AI) technology rapidly advances, its application in pharmaceutical formulation design and Drug Delivery Systems (DDS) is expanding, revealing significant potential. AI technology has played a role in optimizing drug design, enhancing research and development efficiency, and improving the safety profiles of pharmaceutical products, thereby supporting the realization of personalized medicine. This article systematically examines the foundational applications and principles of AI in pharmaceutical formulation, while also evaluating its role in key areas such as drug development, manufacturing, quality control, and ADME/T (absorption, distribution, metabolism, excretion, and toxicity) prediction. In particular, AI can enhance prediction accuracy for drug solubility, stability, and bioavailability, while optimizing novel DDS through Machine Learning (ML) models, such as nanocarrier design and personalized drug release control. Furthermore, AI has been pivotal in advancing intelligent manufacturing technologies, including three-dimensional printing (3D printing) and continuous manufacturing. Finally, the article explores the opportunities and challenges presented by AI in drug development, regulation, and policymaking. Overall, AI's integration promises to revolutionize pharmaceutical development and regulatory practices.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062661","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":"Nanoencapsulation of Essential Oil: A Tailored System of Green Therapeutic Potential.","authors":"Shefali Arora, Sukanya Chhetri, Pankaj Bhandari","doi":"10.2174/0115680266342801250303004033","DOIUrl":"https://doi.org/10.2174/0115680266342801250303004033","url":null,"abstract":"<p><p>Essential oils (EOs) are at the forefront of the pharmaceutical industry today and have been rekindled as natural drugs with innovative techniques. However, many factors related to their volatility and deterioration can be captured by encapsulation. The nanoencapsulation of EO is a novel development to protect EOs from environmental factors in order to retain their biochemical and pharmacological properties, thus leading toward sustainable health advancement. Nanoencapsulation of essential oil (EO) is a fascinating technique to solve the instability problem of EOs in the presence of light, air, moisture, and temperature variations. In addition to this, this process ensures safer handling with controlled release, along with improved efficacy and bioavailability. This review outlines the most outstanding methods for the nanoencapsulation of EOs and their mechanism of action against disease pathogenesis.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983240","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":"Advancements in Herbal Drug Loaded Nanoparticulate System for Antimicrobial Effect.","authors":"Anjali Rana, Arun Mittal, Chetan Vashist, Shivam Rajput, Sathvik Belagodu Sridhar, Sangeet Sharma, Rishabha Malviya","doi":"10.2174/0115680266366494250411164750","DOIUrl":"https://doi.org/10.2174/0115680266366494250411164750","url":null,"abstract":"<p><p>Herbal medicinal compounds have fewer side effects than modern drugs. Herbal materials are primary medicines and have strong antibacterial characteristics, thus most people throughout the world utilize them. Poor solubility, low bioavailability, instability in the biological environment, and substantial first-pass metabolism are some of the challenges associated with delivering plant/herbal medicinal compounds as pharmaceuticals. The use of appropriate nanotechnology for attachment or encapsulation can circumvent these drawbacks of herbal medications. To efficiently administer herbal medications, nanoparticulate formulations such as microemulsions, solid lipid nanoparticles, polymeric nanoparticles, liposomes, and proliposomes are being considered. This article aims to effectively examine the ability of herbal drugs that contain NP to combat microorganisms as well as a variety of herbal plants with antibacterial properties, including thyme, clove, garlic, mallow, chamomile, and mentha pulegium. This comprehensive analysis is timely and necessary since nanotechnology is a promising prospect in infectious disease treatment. Additionally, recent advances in producing herbal medicine formulations based on nanoparticle technologies are also summarised in this review article.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972506","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}