Current topics in medicinal chemistry最新文献

{"title":"In vivo and In Silico Pharmacokinetics Studies on Coumarinolignoid Cliv-92: Unraveling its Effect on Rifampicin-Induced Hepatic Damage.","authors":"Ajay Kumar, Sarfaraz Alam, Sudeep Tandon, Karuna Shanker, Feroz Khan, Dharmendra Saikia","doi":"10.2174/0115680266329609241223114551","DOIUrl":"https://doi.org/10.2174/0115680266329609241223114551","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced hepatotoxicity is a major concern and is caused by all classes of medications, indicating a key area of research. Antitubercular drugs have a beneficial effect but cause hepatotoxicity on prolonged use.</p><p><strong>Aim: </strong>The present work aimed to investigate the role of rifampicin-induced hepatic damage and the effect of Cliv-92 on rifampicin-induced alteration in rats.</p><p><strong>Methods: </strong>Rats were administered with rifampicin, Cliv-92, and silymarin (standard) orally in 0.5% carboxymethyl cellulose (CMC) suspension, in doses of 100 mg/kg, once daily for fourteen days, one hour before the administration of rifampicin. Control animals were treated with 0.5% CMC. On the 14th day, 1hr after the last drug administration, tissue was collected, homogenized, and various parameters, viz. SOD, CAT, GPX, and cytochromes, were estimated from rat liver supernatant and compared with the control group. Blood serum parameters were also measured. Simultaneously, antioxidant activity and in silico studies were performed. The constituent isoforms of Cliv-92 and silymarin and their metabolites were analyzed for different pharmacokinetic characteristics. Silymarin was used as a standard drug.</p><p><strong>Result: </strong>The result of the study suggests that the hepatoprotective potential of Cliv-92 is due to its antioxidant property and inhibitory effect on hepatoproteins, cytochromes (CPY450). An in-silico finding validates the safety profile of Cliv-92, its metabolites, and the standard drug silymarin and also explains that the drug is non-mutagenic.</p><p><strong>Conclusion: </strong>The result of this study indicated that both Cliv-92 and silymarin could be used to avoid drug-induced overload and hepatic damage.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412927","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 Functional Mechanism and Structure-Activity Relationship of Antibacterial Peptides.","authors":"Hanyu Zhong, Xingjun Chen, Sili Han, Linglin Zhang","doi":"10.2174/0115680266350153250121072651","DOIUrl":"https://doi.org/10.2174/0115680266350153250121072651","url":null,"abstract":"<p><p>The escalating growth and global dissemination of antimicrobial resistance underscore the urgency for the discovery of innovative antimicrobial agents. Antibacterial Peptides (AMPs) have emerged as promising candidates, distinctly outperforming conventional antibiotics due to their mitigated propensity for resistance development, expansive antibiofilm activity, and capacity to favorably modulate host immune responses. Consequently, AMPs have garnered significant attention in medical research circles and are anticipated to serve as novel therapeutic alternatives in combating microbial infections, particularly those involving drug-resistant bacteria, thereby inaugurating a novel paradigm in treatment strategies. This comprehensive review delves into the intricate structural and physicochemical attributes of AMPs, providing a concise overview. It further examines the advancements and anticipated clinical trajectories of AMP research, with a pivotal focus on elucidating their antimicrobial mechanisms and the intricate interplay between structure and activity. The aim of this review is twofold: firstly, to enhance the scientific community's comprehension of the antimicrobial mechanisms and Structure-Activity Relationships (SAR) across all classes of AMPs; secondly, to address existing research gaps in the SAR of AMPs, thereby laying a solid foundation for future research endeavors and facilitating the development of these promising therapeutic agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412951","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":"Unveiling the Anticancer Potential of Phytocompounds: Pioneering Future Cancer Therapies.","authors":"Prashant Chauhan, Pratibha Pandey, Seema Ramniwas, Meenakshi Verma, Subbulakshmi Ganeshan, Sumit Rajotiya, Seema Devi, Sorabh Lakhanpal, M Ravi Kumar, Shivam Pandey, Fahad Khan","doi":"10.2174/0115680266354680250121154720","DOIUrl":"https://doi.org/10.2174/0115680266354680250121154720","url":null,"abstract":"<p><p>Cancer epidemiological studies highlight the critical need for identifying better treatment options against cancer. Plants have been widely studied to obtain their efficacy as potent therapeutic agents to treat several diseases, including cancer. Interestingly, some phytocompounds, such as flavonoids, terpenoids, alkaloids, phenolics, and organosulphur compounds [OSCs], have been demonstrating their potential role in combating several pathologies, including the second most devasting disease, cancer, which contributes a significant portion of annual mortality cases. Several in vitro, in vivo, and in silico investigations have recently established remarkable properties of phytocompounds such as antioxidant effects, induction of apoptosis, inhibition of metastasis, autophagy modulation, cell cycle regulation, and chemosensitization that lead to cancer suppression. This underscores the great potential of phytocompounds to contribute as an effective anticancerous drug for the prevention of cancer cases and advancement in cancer research. Therefore, comprehending the complicated mechanism involved in the anticancerous effects of phytocompounds against several carcinomas is crucial to establishing novel therapeutic strategies. Thus, this review tends to summarize the involvement of the most promising classes of phytompounds in cancer management and highlights several clinical trial data that demonstrate significant results in managing diverse carcinomas.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413234","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":"Progress in Synthetic Approaches and Pharmacological Applications of Melatonin and Its Derivatives: A Comprehensive Review.","authors":"Ayush Jain, Chandana Majee, Rupa Mazumder, Avijit Mazumder, Himanshu Singh, Swrupanjali Padhi, Arvind Kumar, Bhupinder Kapoor","doi":"10.2174/0115680266331681250130072302","DOIUrl":"https://doi.org/10.2174/0115680266331681250130072302","url":null,"abstract":"<p><p>A neurohormone with strong central nervous system activity, melatonin plays a role in regulating circadian rhythms. It affects practically all tissues and organs and has a broad functional repertoire. It is primarily employed as a dietary supplement; melatonin aids in sleep regulation and the re-establishment of arousal cycles. Despite having very low toxicity, melatonin's tissue availability is constrained by pharmacokinetic problems such as poor oral bioavailability and a brief half-life. The synthesis and medicinal applications of melatonin and its derivatives are the main focus of this review study. Melatonin is considered as a beneficial agent suitable for safely treating and preventing various health conditions. This review covers synthesis approaches and pharmacological applications of melatonin and its derivatives published from the 1990s to 2024. The latest development in several studies involves the concurrent administration of melatonin with other drugs to enhance therapeutic effectiveness and mitigate adverse effects. Hybrid ligands, such as melatonin-tamoxifen and melatonin-tacrine derivatives are combined to give distinct effects. This review highlights the importance of continued research into melatonin and its derivatives, paving the way for developing novel and more potent therapeutic agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398608","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":"Innovative Therapies: A Major Breakthrough in Combating Multi-Drugresistant Bacterial Infections Using Mixture Design and Multi-Objective Optimization with NSGA-II Algorithm.","authors":"Meriem Adouane, Nabil Kadri, Nourelimane Benzitoune, Chafika Lakhdari, Samia Djellal, Lilla Ousmer, Hichem Tahraoui, Abdeltif Amrane, Hocine Remini, Farid Dahmoune, Khodir Madani","doi":"10.2174/0115680266333406250126033304","DOIUrl":"https://doi.org/10.2174/0115680266333406250126033304","url":null,"abstract":"<p><strong>Introduction/objective: </strong>The increasing resistance of pathogens to antibiotics poses a major public health challenge. This study aims to develop an innovative approach to combat this resistance by exploring synergies between standard antibiotics and marine metabolites.</p><p><strong>Methods: </strong>The methodology combines disk diffusion testing and mixture design to assess the antimicrobial efficacy of the combinations.</p><p><strong>Results: </strong>The results demonstrate promising synergies between carotenoids, polyphenols, and alkaloids with standard antibiotics, offering potential targeted use in the fight against clinical multidrug- resistant bacteria. Specifically, Gram-negative bacteria (BGN) showed increased resistance to antibiotics such as amoxicillin-clavulanic acid (AMC), ceftazidime, cefotaxime, tetracycline, and cefazolin. These antibiotics, when combined with marine compounds, exhibited substantial inhibitory effects against specific isolates, circumventing antibiotic resistance mechanisms. Similarly, substantial synergies were observed in Gram-positive bacteria. Leveraging advanced algorithms such as multi-objective optimization, notably the NSGA-II algorithm, we accurately predicted minimum inhibitory concentrations (MICs) against clinically resistant bacterial isolates. Optimal conditions against Escherichia coli, characterized by carotenoids = 0.6335, total polyphenols = 0, indole alkaloids = 0.1723, and AMC = 0.1941, yielded a predicted MIC of 41.1126 mg/L, closely mirroring the experimental MIC of 41.66 ± 0.18 mg/L. Similarly, for Staphylococcus aureus, optimal conditions produced a predicted MIC of 30.8304 mg/L, closely aligning with the experimental MIC of 30.69 ± 1.80 mg/L.</p><p><strong>Conclusion: </strong>The consistent and reliable predictions for bacterial strains affirmed the robustness of the applied methodology. These results not only pave the way for further exploration but also offer valuable insights for optimizing pharmaceutical and medical interventions, presenting innovative avenues for combating antibiotic-resistant bacterial infections.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398601","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":"Strategies to Combat Resistance to Anti-angiogenesis Therapies in Cancer: Current Status and Future Prospects.","authors":"Vijay K Patel, Ekta Shirbhate, Vaibhav Singh, Shadiya Parveen, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak","doi":"10.2174/0115680266324868250123052818","DOIUrl":"https://doi.org/10.2174/0115680266324868250123052818","url":null,"abstract":"<p><p>Anti-angiogenic therapy represents a promising approach to cancer treatment by targeting the vascular support systems of tumors rather than the tumor cells themselves. Antiangiogenic agents face numerous obstacles that impede their efficacy, notwithstanding their potential: mechanistic complexity, toxicity, resistance, and the lack of validated predictive biomarkers. Resistance mechanisms may encompass genetic modifications, alternative angiogenic pathways, or the recruitment of cells derived from bone marrow. This work examines present problems and approaches to overcome resistance against anti-angiogenic treatment. Treatment response is predicted by biomarker-guided therapy; patterns of circulating endothelial cells, IL-8 levels, and VEGFR expression indicate possible therapeutic monitoring value. Multi-targeted approaches including drugs that block VEGFR, PDGFR, FGFR, and c-MET concurrently have shown more efficacy than single- pathway inhibition. Additional research indicates that combining treatments has positive results. Combining anti-angiogenic agents with cancer vaccines increases immune responses and tumour regulation. Combining radiotherapy with chemotherapy increases drug delivery and efficacy utilizing vascular normalisation. Techniques based on nanotechnology such as gold nanoparticles and carbon-based materials may enhance medicinal efficacy and delivery. These results reveal that to overcome resistance mechanisms and enhance patient outcomes anti-angiogenic therapy must combine focused therapies with precision medicine approaches.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398615","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":"Review on the Phytochemistry and Pharmacological Potential of Saffron (Crocus sativus L.).","authors":"Sonia Singh, Khushi Sharma","doi":"10.2174/0115680266352428250130112654","DOIUrl":"https://doi.org/10.2174/0115680266352428250130112654","url":null,"abstract":"<p><p>Saffron has been used in Chinese medicine for a very long time, dating back to 1979, when it was first brought inside of China. According to Traditional Chinese medicine, saffron has a sweet, moderately chilly character, and it has remarkable effects on the liver and heart systems. In addition, this spice stimulates blood circulation, removes blood stasis, reduces blood temperature, and eradicates heat-related toxins. The herb has been used to treat a variety of conditions, including pain, hemoptysis, asthma, phlegm, sleeplessness, depression, anxiety, and Alzheimer's disease. Saffron has over seventy different bioactive components, the most important of which are crocin, crocetin, and safranal. These three components are responsible for the distinctive color and flavor of saffron. This article briefly covers the phytochemistry and pharmacological potential of this uncommon herb.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122385","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":"Targeted Photodynamic Therapy for Drug-Resistant Pulmonary Tuberculosis through Mycolic Acid and Cyclohexadiene-Aminophenyl Interactions.","authors":"Anwesha Sahu, Satyajit Mohanty, Tuhin Mukherjee","doi":"10.2174/0115680266371708250131062447","DOIUrl":"https://doi.org/10.2174/0115680266371708250131062447","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122386","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":"A Recent Progress in Biological Activities of 1,3,4-thiadiazole and its Derivatives: A Review.","authors":"Sarah Chandurwala, Hardha Balachandran, B Gowramma, Yokkesh M, Vishal Pranav, J Vinethmartin, Aryan Jangra, Sowmiya Arun, Kaviarasan L","doi":"10.2174/0115680266344588241127031534","DOIUrl":"https://doi.org/10.2174/0115680266344588241127031534","url":null,"abstract":"<p><p>1,3,4-thiadiazole can be produced in several ways and has a wide range of possible biological uses. As a result, scientists have created novel procedures for producing 1,3,4-thiadiazole derivatives and their use in medicine. Among the activities are Anticancer, anticonvulsant, antimicrobial, antifungal, antiinflammatory, antiHIV, antidiabetic, antitubercular, antifungal, and other properties. We have compiled different biological activities of 1,3,4-thiadazole in this review study. Many researchers may find the material on this page helpful, which could result in the identification of new medicinal species beneficial to society.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122375","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":"Therapeutic Potential of Simvastatin: Cellular Mechanism, Binding Energetics, and Resistance Developments.","authors":"Shristy Verma, Rishabha Malviya, Sonali Sundaram, Saurabh Srivastava, Sathvik Belagodu Sridhar, Safia Obaidur Rab, Deependra Pratap Singh","doi":"10.2174/0115680266327892241223052456","DOIUrl":"https://doi.org/10.2174/0115680266327892241223052456","url":null,"abstract":"<p><p>Statins are a class of hypolipidemic agents that have been shown to promote osteogenic differentiation through enhanced alveolar bone recovery, inserted osseointegration, and cartilage regeneration. This review uses Molecular Docking (MD) simulations and additional Computer- Aided Drug Design (CADD) methods to present the state of the art in statin therapy. Furthermore, several studies have shown that factors such as limited overall absorption, metabolism in the first pass, and systemic side effects are among those that affect the oral administration of statins. In addition, these variables include susceptibility to efflux mechanisms, drug permeability, dissolution percentage, aqueous solubility, initial metabolism, and pre-systemic metabolism. Additionally examined are the pharmacokinetics of the statin and in vivo mechanisms of action. As a result of the numerous problems associated with the consumption of statins, including their low total bioavailability, first-pass metabolism, low aqueous solubility, and systemic adverse reactions, a non-oral mode of administration was looked into for this crucial and primary class of pharmacokinetic agents. However, to optimize bioavailability and minimize side effects, more research is required.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122387","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}