Current topics in medicinal chemistry最新文献

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Antimicrobial Plant Peptides: Structure, Classification, Mechanism And Therapeutic Potential.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-03-17 DOI: 10.2174/0115680266345963250121112522
Shaina Shahab Khan, Suaib Luqman
{"title":"Antimicrobial Plant Peptides: Structure, Classification, Mechanism And Therapeutic Potential.","authors":"Shaina Shahab Khan, Suaib Luqman","doi":"10.2174/0115680266345963250121112522","DOIUrl":"https://doi.org/10.2174/0115680266345963250121112522","url":null,"abstract":"<p><p>Humans, animals, and plants possess small polypeptides known as antimicrobial peptides (AMPs), which are often positively charged. They are tiny, mostly basic peptides with a molecular weight of 2 to 9 kDa. They are a crucial part of plants' innate defense system, acting as effector molecules that provide a resistance barrier against pests and diseases. Plants have been found to contain antimicrobial peptides belonging to numerous families, including plant defensins, thionins, cyclotides, and others. An increase in pathogen resistance is achieved through the transgenic overexpression of the relevant genes, while pathogen mutants that are susceptible to peptides exhibit decreased pathogenicity. For many organisms, AMPs exhibit a wide range of antimicrobial activity against various pathogens and serve as a crucial line of defense. This review raises awareness about plant antimicrobial peptides (AMPs) as potential therapeutic agents in the pharmaceutical and medical fields, including treating fungal and bacterial diseases. It also provides a broad synopsis of the main AMP families found in plants, their mechanisms of action, and the factors that influence their antimicrobial activities.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655984","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}
引用次数: 0
Effect of Recombinant Tuxtide Intervention on DSS-induced Acute UC Mouse Model.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-03-17 DOI: 10.2174/0115680266343609250226094349
Min Zhou, Yi Yang, Zhuoling Wang, Yu Gao, Dongmei Dang, Xiaochan He, Changwu Yue
{"title":"Effect of Recombinant Tuxtide Intervention on DSS-induced Acute UC Mouse Model.","authors":"Min Zhou, Yi Yang, Zhuoling Wang, Yu Gao, Dongmei Dang, Xiaochan He, Changwu Yue","doi":"10.2174/0115680266343609250226094349","DOIUrl":"https://doi.org/10.2174/0115680266343609250226094349","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to investigate the differences in the therapeutic effects of recombinant GLP-2 and Lactobacillus plantarum L9, both alone and in combination, for treating UC, providing new directions for future acute UC therapy.</p><p><strong>Methods: </strong>The GLP-2 homologous peptide from Amphiuma tridactylum species was screened via the NCBI database, and its advanced structure and molecular function were bioinformatically predicted. This fragment was then recombined into the plasmid pET-28a (+) and transformed into Escherichia coli Rosetta (BL21). IPTG induced the expression of the recombinant protein, which was purified, followed by thrombin cleavage to obtain Tuxtide peptides. These peptides were separated via Native PAGE and purified using Trition X-114 and dialysis methods. Acute UC model mice were established using 3% DSS. Changes in body weight and disease activity index scores during the medication period were recorded and analyzed. Colon length and spleen index of mice in each group were measured, and HE staining and colon histology scoring were performed. ELISA was used to detect myeloperoxidase and interleukin-1β in mouse colon tissue.</p><p><strong>Results: </strong>Compared to the DSS group, the colon length of mice in all treatment groups improved, with significant effects observed in the Tuxtide and Tuxtide+L9 groups (P<0.05). Body weight in all treatment groups rebounded compared to the DSS group, and DAI scores decreased (P<0.05), with the Tuxtide group showing the best improvement in body weight. All treatment groups alleviated intestinal mucosal pathological damage to varying degrees compared to the DSS group, with the Tuxtide+L9 group showing the best anti-inflammatory effect, reducing colon histology scores and restoring intestinal crypts (P<0.1).</p><p><strong>Conclusion: </strong>Both Tuxtide alone and in combination with Lactobacillus plantarum L9 can alleviate symptoms in mice with acute ulcerative colitis.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656018","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}
引用次数: 0
Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-03-07 DOI: 10.2174/0115680266340314250303003647
Chenglong Wu, Leyao Jiang, Ying Zhong, Zongliang Liu
{"title":"Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.","authors":"Chenglong Wu, Leyao Jiang, Ying Zhong, Zongliang Liu","doi":"10.2174/0115680266340314250303003647","DOIUrl":"https://doi.org/10.2174/0115680266340314250303003647","url":null,"abstract":"<p><p>Cancer and Alzheimer's disease (AD) are among the most prevalent diseases in contemporary society, exerting profound psychological and physical distress on affected individuals and their kin. There is an emerging consensus from epidemiological studies suggesting a potential inverse relationship between the two conditions; that is, the presence of one disease might offer some level of protection against the other. The etiology of both cancer and AD is intricately linked to dysregulation and perturbations in critical signaling pathways. These pathways, along with the diverse factors they encompass, exert distinct influences on the pathogenesis of two diseases. In this paper, we make a short review of the different mutations in the relevant signaling pathways between cancer and AD and introduce a few representative drugs for the two diseases based on various targets to provide a new idea for treating cancer and AD.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585020","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}
引用次数: 0
The Impact and Role of Artificial Intelligence (AI) in Healthcare: Systematic Review.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-03-03 DOI: 10.2174/0115680266339394250225112747
Kavya Singh, Ashish Prabhu, Navjeet Kaur
{"title":"The Impact and Role of Artificial Intelligence (AI) in Healthcare: Systematic Review.","authors":"Kavya Singh, Ashish Prabhu, Navjeet Kaur","doi":"10.2174/0115680266339394250225112747","DOIUrl":"https://doi.org/10.2174/0115680266339394250225112747","url":null,"abstract":"<p><strong>Introduction: </strong>Healthcare organizations are complicated and demanding for all stakeholders, but artificial intelligence (AI) has revolutionized several sectors, especially healthcare, with the potential to enhance patient outcomes and standard of life. Quick advancements in AI can transform healthcare by implementing it into clinical procedures. Reporting AI's involvement in clinical settings is vital for its successful adoption by providing medical professionals with the necessary information and tools.</p><p><strong>Background: </strong>This paper offers a thorough and up-to-date summary of the present condition of AI in medical settings, including its possible uses in patient interaction, treatment suggestions, and disease diagnosis. It also addresses the challenges and limitations, including the necessity for human expertise along with future directions. In doing so, it improves the understanding of AI's relevance in healthcare and supports medical institutions in successfully implementing AI technologies.</p><p><strong>Methods: </strong>The structured literature review, with its dependable and reproducible research process, allowed the authors to acquire 337 peer-reviewed publications from indexing databases, such as Scopus and EMBASE, without any time restrictions. The researchers utilized both qualitative and quantitative factors to assess authors, publications, keywords, and collaboration networks.</p><p><strong>Results: </strong>AI implementation in healthcare holds enormous potential for enhancing patient outcomes, treatment recommendations, and disease diagnosis. AI technologies can use massive datasets and recognize patterns to beat human performance in various healthcare domains. AI provides improved accuracy, reduced expenses, and time savings. It can transform customized medicine, optimize drug dosages, improve management of population health, set guidelines, offer digital medical assistants, promote mental health services, boost patient knowledge, and maintain patientclinician trust.</p><p><strong>Conclusion: </strong>AI can be utilized to detect diseases, develop customized therapy plans, and support medical professionals with their clinical decision-making. Instead of just automating jobs, AI focuses on creating technologies that can improve patient care in several healthcare settings. However, challenges such as biasness, data confidentiality, and data quality must be resolved for the appropriate and successful integration of AI in healthcare.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540341","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}
引用次数: 0
Chemical Profiling and Antibacterial Potential of Methanol Extract of Solanum xanthocarpum Fruits against Methicillin-Resistant Staphylococcus aureus: Implications for AMR Management.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-03-03 DOI: 10.2174/0115680266364747250223154131
Akshaya Rani Augustus, Yashwanth Radhakrishnan, James Prabhanand Bhaskar, Suresh Ramamurthi, Karutha Pandian Shunmugiah
{"title":"Chemical Profiling and Antibacterial Potential of Methanol Extract of Solanum xanthocarpum Fruits against Methicillin-Resistant Staphylococcus aureus: Implications for AMR Management.","authors":"Akshaya Rani Augustus, Yashwanth Radhakrishnan, James Prabhanand Bhaskar, Suresh Ramamurthi, Karutha Pandian Shunmugiah","doi":"10.2174/0115680266364747250223154131","DOIUrl":"https://doi.org/10.2174/0115680266364747250223154131","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the antimicrobial potential of methanol fruit extract of Solanum xanthocarpum against Methicillin-Resistant Staphylococcus aureus (MRSA) and elucidate its mode of action.</p><p><strong>Background: </strong>The rise of antimicrobial resistance (AMR) demands the exploration of alternative therapeutic strategies to combat resistant pathogens.</p><p><strong>Objective: </strong>To evaluate the efficacy of Solanum xanthocarpum methanol extract against MRSA, and identify its active constituents and mechanism of action.</p><p><strong>Method: </strong>The fruits of Solanum xanthocarpum were extracted using various solvents, with hexane and methanol yielding the highest results. Microbroth dilution assays assessed antimicrobial activity, while in vitro assays such as Alamar blue, Scanning Electron Microscopy (SEM), protein, and nucleic acid leakage examined metabolic disruption and cell membrane integrity. Gas Chromatography- Mass Spectrometry (GC-MS) was used to identify active compounds, and molecular docking studies assessed interactions with key MRSA proteins.</p><p><strong>Result: </strong>The methanol extract demonstrated significant antimicrobial activity against MRSA, causing metabolic disruption and leakage of cellular contents as evidenced by various in vitro assays including alarm blue, SEM, and protein and nucleic acid leakage assay. GC-MS analysis identified alpha-linoleic acid and palmitic acid as key active components. Molecular docking studies confirmed their inhibition of beta-lactamase activity, cell wall biosynthesis, efflux pumps, and virulence factors.</p><p><strong>Conclusion: </strong>The findings suggest that Solanum xanthocarpum methanol fruit extract has promising potential as a natural remedy against AMR associated with MRSA.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540424","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}
引用次数: 0
Application of Artificial Intelligence-Based Approaches in the Discovery and Development of Protein Kinase Inhibitors (PKIs) Targeting Anticancer Activity.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-02-28 DOI: 10.2174/0115680266340766250124063854
Emanuelly Karla Araújo Padilha, Wadja Feitosa Dos Santos Silva, Arestides Alves Lins, Edeildo Ferreira da Silva-Júnior
{"title":"Application of Artificial Intelligence-Based Approaches in the Discovery and Development of Protein Kinase Inhibitors (PKIs) Targeting Anticancer Activity.","authors":"Emanuelly Karla Araújo Padilha, Wadja Feitosa Dos Santos Silva, Arestides Alves Lins, Edeildo Ferreira da Silva-Júnior","doi":"10.2174/0115680266340766250124063854","DOIUrl":"https://doi.org/10.2174/0115680266340766250124063854","url":null,"abstract":"<p><p>Herein, we present an in-depth review focused on the application of different artificial intelligence (AI) approaches for developing protein kinase inhibitors (PKIs) targeting anticancer activity, focusing on how the AI-based tools are making promising advances in drug design and development, by predicting active compounds for essential targets involved in cancer. In this context, the machine learning (ML) approach performs a critical role by promoting a fast analysis of a thousand potential inhibitors within a small gap of time by processing large datasets of chemical data, putting it at a higher level than other traditionally used methods for screening molecules. In general, AI-based screening of compounds reduces the time of the work and increases the chances of success in the end. Additionally, we have covered recent studies focused on the application of deep neural networks (DNNs) and quantitative structure-activity relationships (QSAR) to identify PKIs. Furthermore, the paper covers new AI-based methodologies for filtering or improving datasets of potential compounds or even targets, such as generative models for the creation of novel compounds and ML-based strategies to collect information from different databases, increasing the efficiency in drug design and development. Finally, this review highlights how AI-based tools are increasing and improving the field of PKIs targeting cancer, making them an alternative for the future in the medicinal chemistry field.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540306","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}
引用次数: 0
Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-02-27 DOI: 10.2174/0115680266319955241224073611
Bethsebie Lalduhsaki Sailo, Ravichandran Vishwa, Sosmitha Girisa, Babu Santha Aswani, Mohamed Abbas, Mohammed S Alqahtani, Hassan Ali Almubarak, Mangala Hegde, Ajaikumar B Kunnumakkara
{"title":"Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.","authors":"Bethsebie Lalduhsaki Sailo, Ravichandran Vishwa, Sosmitha Girisa, Babu Santha Aswani, Mohamed Abbas, Mohammed S Alqahtani, Hassan Ali Almubarak, Mangala Hegde, Ajaikumar B Kunnumakkara","doi":"10.2174/0115680266319955241224073611","DOIUrl":"https://doi.org/10.2174/0115680266319955241224073611","url":null,"abstract":"<p><p>Genistein (GEN), a phytoestrogen primarily sourced from soy plants, is recognized for its anticancer properties attributed to its roles as a tyrosine kinase inhibitor, an estrogen receptor agonist, and its influence on various cancer hallmarks by modulating diverse signaling pathways. Recent research has highlighted the considerable potential of GEN in combating drug resistance in cancer cells. This attribute of GEN has been demonstrated by its capacity to modulate tyrosine kinases such as HER2, HER3, and EGFR which are implicated in tumorigenesis, as well as prosurvival signaling pathways including NF-κB and Akt/mTOR. Moreover, GEN impacts drug accumulation, AR-driven transcriptional regulation, ER signaling, and various genes that are involved in autophagy, pro/anti-apoptosis, DNA methylation, and histone acetylation. Further, GEN demonstrated efficacy in combinatorial therapy with various standard anticancer agents like 5-FU, cetuximab, cisplatin, clofarabine, doxorubicin, tamoxifen, TRAIL, trastuzumab, and other agents with anticancer activities such as capsaicin, curcumin, daidzein, lycopene, resveratrol, sulforaphane, etc., across a spectrum of cancers including the cancers of bone, brain, breast, cervix, colorectal, endometrium, esophagus, head and neck, leukemia, liver, lung, ovary, pancreas and stomach. Thus, further clinical validation of these potential combinations involving GEN is warranted to confirm the preclinical findings.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522921","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}
引用次数: 0
Diverse Therapeutic Potentials of Hypericin: An In-Depth Review.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-02-27 DOI: 10.2174/0115680266330142250224101958
Sandeep Kumar Maurya, Sheetal Divakar, Sunny Rathee, Umesh Kumar Patil
{"title":"Diverse Therapeutic Potentials of Hypericin: An In-Depth Review.","authors":"Sandeep Kumar Maurya, Sheetal Divakar, Sunny Rathee, Umesh Kumar Patil","doi":"10.2174/0115680266330142250224101958","DOIUrl":"https://doi.org/10.2174/0115680266330142250224101958","url":null,"abstract":"<p><strong>Background: </strong>This review is delving into determining the content and significance of hypericin, a pharmacologically important constituent commonly known as St. John's Wort (SJW). The paper explores the rich history of Hypericin's traditional use in alternative medicine and the recent surge in scientific interest surrounding its bioactive properties.</p><p><strong>Objective: </strong>This review aims to comprehensively analyse the therapeutic potentials of hypericin, focusing on its chemistry, extraction, sources, stability, pharmacokinetics, safety profile, and multifunctional applications in drug and medicinal fields as well as advancements in Bioengineering Approaches for Enhanced Hypericin Delivery.</p><p><strong>Methods: </strong>We performed a non-systematic search of journals. Literature using computerized methods was conducted, utilizing databases such as Medline (PubMed), ChemSciFinder, China National Knowledge Infrastructure (CNKI) and Scirus Library. To effectively identify the most important and relevant research articles, scientific studies, clinical studies and review articles on hypericin were searched using different keywords: \"Hypericum\", \"traditional use\", \"phytochemistry\", \"pharmacology\", \"drug delivery\" and \"bioactivity\". Thus, articles available from 1984 to 2024 were analyzed and collected. The selection process for the review primarily considered the originality of the paper and its clinical applications.</p><p><strong>Results: </strong>Although hypericin is not a novel compound within the research community, it is gaining renewed recognition and showing great effectiveness as a promising agent in the field of medical diagnostics and has promising applications as a therapeutic.</p><p><strong>Conclusion: </strong>Here, our current comprehensive review of hypericin, its potential and its activities is intended to contribute to this ongoing process actively. Overall, this review provided theoretical direction for future hypericin research. Future studies should, therefore, focus further on the pharmacological processes, pharmacokinetics, and chemistry of hypericin and hypericin-based drug delivery systems. Our most recent overview of hypericin's functions and potentials is meant to aid in this process.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522908","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}
引用次数: 0
A Comprehensive Review on the Antimicrobial Activity of the Genus Artemisia, Artemisinin, and its Derivatives.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-02-27 DOI: 10.2174/0115680266343676250122062731
Kiran Sharma
{"title":"A Comprehensive Review on the Antimicrobial Activity of the Genus Artemisia, Artemisinin, and its Derivatives.","authors":"Kiran Sharma","doi":"10.2174/0115680266343676250122062731","DOIUrl":"https://doi.org/10.2174/0115680266343676250122062731","url":null,"abstract":"<p><p>Artemisinin and its semisynthetic derivatives are a group of bioactive chemicals obtained mostly from the extracts of Artemisia species that exert a significant amount of antimalarial activity while remaining relatively safe and tolerable. However, their effectiveness is not limited to malaria; it extends to a variety of human infectious diseases. Mostly the mode of action includes the generation of free radicals by breaking the endoperoxide link in its molecular structure, which facilitates the eradication of microbial species. Artemisinins are found to inhibit bacterial, viral, protozoal, helminth, and fungal infections. Their derivatives, like artemisone, a reversible inhibitor, target the viral replication cycle, and artesunate suppresses EBV infection by inhibiting the production of early EBV proteins. They were also found to be highly effective against Helicobacter pylori and Mycobacterium tuberculosis by generating peroxides in a time and concentrationdependent way. Other derivatives, such as artesunate, artemether, and arteether, have also shown antimicrobial activity that can be administered orally, rectally, intramuscularly, or intravenously. This review aims to provide a complete update on the antimicrobial applications of Artemisinin and its semi-synthetic derivatives, as well as derived dimers/trimers. The paper reflects a significant potential for the discovery of novel Artemisinin medications that can be used as supplementary treatments for various diseases. However, further translational and experimental research is required for optimization and the establishment of pharmacokinetic profiles. In addition, health authorities are also required to regulate the present Artemisinins and newly discovered derivatives to ensure their long-term effectiveness in the worldwide fight against antibiotic resistance.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522906","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}
引用次数: 0
Computational Identification and Anti-Inflammatory Evaluation of T19093 as a TLR4/MD2 Inhibitor.
IF 2.9 4区 医学
Current topics in medicinal chemistry Pub Date : 2025-02-18 DOI: 10.2174/0115680266345918250212144023
Kuida Chen, Ke Shi, Tong Jin, Shipeng Lu, Wu Yin
{"title":"Computational Identification and Anti-Inflammatory Evaluation of T19093 as a TLR4/MD2 Inhibitor.","authors":"Kuida Chen, Ke Shi, Tong Jin, Shipeng Lu, Wu Yin","doi":"10.2174/0115680266345918250212144023","DOIUrl":"https://doi.org/10.2174/0115680266345918250212144023","url":null,"abstract":"<p><strong>Background: </strong>The TLR4 (Toll-like receptor 4)/MD2 (Myeloid differentiation protein-2) is a crucial target for developing novel anti-inflammatory drugs. Nevertheless, current inhibitors often have significant adverse effects, necessitating the discovery of safer alternatives.</p><p><strong>Objective: </strong>The investigation aims to identify novel TLR4/MD2 inhibitors with potential antiinflammatory activity using machine learning and virtual screening technology.</p><p><strong>Methods: </strong>A machine-learning model was created using the MACCS (Molecular ACCess Systems) key fingerprint. Subsequently, virtual screening and molecular docking were used to evaluate candidate compounds' binding free energy to the TLR4/MD2 complex. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction was used to assess the druggable properties of compounds. The most promising compound, T19093, was considered for molecular dynamic simulation. Finally, the anti-inflammatory efficacy of T19093 was further validated using LPS-treated THP-1 cells.</p><p><strong>Results: </strong>T19093, a polyphenolic compound isolated from the Gnaphalium plant genus, showed strong binding to key residues of the TLR4/MD2 complex, with a docking score of -11.29 kcal/mol. Furthermore, ADMET predicted that T19093 has good pharmacokinetic properties and balanced physicochemical properties. Moreover, molecular dynamics simulation confirmed stable binding between T19093 and TLR4/MD2 complex. Finally, it was found that T19093 alleviated LPSinduced inflammatory response by inhibiting the activation of TLR4/MD2 downstream signaling pathways and disrupting the TLR4/MD2 interaction.</p><p><strong>Conclusion: </strong>T19093 was discovered as a potential novel TLR4/MD2 inhibitor using machine learning and virtual screening techniques and showed potent anti-inflammatory activity, which could provide a new therapeutic alternative for the treatment of inflammation-related diseases.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457177","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}
引用次数: 0
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