Current topics in medicinal chemistry最新文献

{"title":"Conformation Study and Design of Novel 6-Hydroxybenzothiazole-2-Carboxamides as Potentially Potent and Selective Monoamine Oxidase B Inhibitors for Neuroprotection.","authors":"Dong Xie, Penghang Guo, Quantang Zhao, Yu Gao, Jianan Zhang, Jie Zhou","doi":"10.2174/0115680266354743241216065502","DOIUrl":"https://doi.org/10.2174/0115680266354743241216065502","url":null,"abstract":"<p><strong>Background: </strong>6-hydroxybenzothiazole-2-carboxamide is a novel, potent, and specific monoamine oxidase B inhibitor that can be used to study the structure of molecules and come up with new ways to protect neurons.</p><p><strong>Objective: </strong>The objective of this work was to create an effective model using derivatives of 6- hydroxybenzothiazole-2-carboxamide and establish a dependable predictive foundation for the development of neuroprotective monoamine oxidase B inhibitors for the treatment of neurodegenerative diseases.</p><p><strong>Methods: </strong>The construction and optimization of all compounds were carried out sequentially using ChemDraw software and Sybyl-X software. The optimized compounds were further analyzed using the COMSIA approach and the Sybyl-X software tool for QSAR modeling. A set of novel compounds of 6-hydroxybenzothiazole-2-carboxamide were created and their IC50 values were forecasted using QSAR modeling. Ultimately, the recently developed compounds underwent a screening process using their IC50 values, and molecular docking tests were conducted on the ten most promising compounds with the highest IC50 values.</p><p><strong>Results: </strong>The 3D-QSAR model exhibited favorable outcomes. The value of q2 in the COMSIA model was 0.569. The model demonstrated a superior r2 value of 0.915, a lower SEE of 0.109, and a higher F-value of 52.714. The statistical findings and validation of the model were deemed adequate. Furthermore, analyzing the contour plots might assist in identifying the necessary structural specifications.</p><p><strong>Conclusion: </strong>This work has the potential to provide an insight into the development of active medicines that protect the nervous system against neurodegenerative disorders.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982151","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":"100 Years of Insulin: A Historical Perspective.","authors":"Gabrielle Barbosa Pinto, Ivaldo Itabaiana Junior, Jorge Lima Magalhães, Adelaide Maria de Souza Antunes","doi":"10.2174/0115680266315941241127092613","DOIUrl":"https://doi.org/10.2174/0115680266315941241127092613","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus, a metabolic disease characterized by high blood glucose levels, has increased dramatically in recent years, prompting the need for more affordable diagnoses and treatments.</p><p><strong>Objective: </strong>This study aimed to conduct a brief historical and theoretical review on the development of insulin.</p><p><strong>Methods: </strong>Scientific and technological data have been retrieved and analyzed with a focus on the development of the active pharmaceutical ingredient insulin and insulin-based medicines. Data have been retrieved from the PubMed database available via the CAPES portal.</p><p><strong>Results: </strong>Diabetes is one of the oldest diseases in the world. The year 2021 marked the 100th anniversary of the discovery of insulin, which transformed diabetes from a fatal disease into a chronic disease. The extraction and purification of insulin from bovine or porcine pancreases from slaughterhouses has enabled the pharmaceutical industry to produce insulin on a large scale. The introduction of insulin analogs in 1996 expanded the options. Currently, commercial insulin consists of human insulin and/or human insulin analogs.</p><p><strong>Conclusion: </strong>The state-of-the-art and technological development of insulin over the last 100 years has been presented in this work. The development of new pharmaceutical technologies has led to the obtainment of improved versions of insulin, as well as the emergence of different types of insulin. Alongside the innovations in the development of the active ingredient and related medicines, new formulations, methods, and routes of administration have emerged based on the pharmacodynamic, pharmacokinetic, and pharmacotechnical modulations of the drug.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982148","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":"Synthetic Strategies for the Development of Ibuprofen Derivatives: A Classified Study.","authors":"Kuchana Madhavi, Barla Karuna Devi","doi":"10.2174/0115680266334717241127043711","DOIUrl":"10.2174/0115680266334717241127043711","url":null,"abstract":"<p><p>Ibuprofen, a widely used NSAID from the aryl propionic acid class, effectively relieves pain, fever, and inflammation. On prolonged use, it leads to gastrointestinal, hepatic, and renal toxicities, particularly gastrointestinal ulcers. These side effects are largely attributed to the carboxylic acid functional group common to NSAIDs. The present review highlights the different modifications done to the carboxylic group in Ibuprofen, by various researchers such as esters, amides, hydroxamic acids, and N-substituted hydrazides, along with the integration of heterocyclic moieties like triazoles, tetrazoles, and oxadiazoles. Additionally, Ibuprofen has been hybridized with other drugs and complexed with metals to enhance therapeutic effects. The different synthetic strategies that were employed were esterification, amidation, condensation, Schiff’s base formation, etc. These modifications have resulted in derivatives with antimicrobial, antifungal, anticancer, and other biological activities, aiming to reduce side effects while retaining or enhancing anti-inflammatory, analgesic, and antipyretic properties.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982639","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":"Traditional Chinese Medicine for Liver Cancer Treatment: Network Pharmacology Research.","authors":"Shihao Zheng, Yixiao Gu, Wenying Qi, Wei Wang, Xiaoke Li, Xiaobin Zao, Size Li, Shaoyu Liu, Tianyu Xue, Yongan Ye, Aimin Liu","doi":"10.2174/0115680266336478241118065659","DOIUrl":"https://doi.org/10.2174/0115680266336478241118065659","url":null,"abstract":"<p><strong>Background: </strong>As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of action has not yet been clarified.</p><p><strong>Aim: </strong>This study reviews the current status and characteristics of network pharmacology research in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese medicine treatment of the disease.</p><p><strong>Methods: </strong>This study was searched on the Web of Science and PubMed using keywords, such as \"traditional Chinese medicine\", \"liver cancer,\" and \"network pharmacology.\" The citation dates of the literature cited in this review are from 2000 to 2024.</p><p><strong>Results: </strong>The discovery of the key molecular mechanisms of traditional Chinese medicine in the treatment of liver cancer through the network pharmacology approach and the in-depth study of the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese medicine.</p><p><strong>Conclusion: </strong>Network pharmacology research plays a key role in the treatment and prevention of liver cancer and deserves deeper exploration in the future.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978019","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":"Bioanalysis, Analysis, Chemistry, and Pharmacological Aspects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors.","authors":"Sunidhi Jain, Roshani Patil, Sanjay Sharma","doi":"10.2174/0115680266324419241227102847","DOIUrl":"https://doi.org/10.2174/0115680266324419241227102847","url":null,"abstract":"<p><p>The development of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIFPHIs), such as Roxadustat (ROX), Enarodustat (ENA), Desidustat (DES), Vadadustat (VAD), Molidustat (MOL), and Daprodustat (DAP), has significant effects on anemia in chronic kidney disease. This review presents comprehensive information about the synthesis, pharmacology, and analysis of HIF-PHIs across several matrices. The literature has presented several approaches for quantifying HIF-PHIs in diverse sample matrices. Furthermore, HIF-PHIs exhibit similar modes of action, demonstrating distinct pharmacokinetic parameters. The pharmacological insights encompass their half-life, mechanism of action, absorption, distribution, metabolism, excretion, and therapeutic uses. Research indicates that most studies concentrate on hyphenated methodologies for drug estimation in various biological fluids. Consequently, this study assesses the biological efficacy of HIF-PHIs and elucidates the analytical methodologies currently employed for measurement across various matrices.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946157","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":"Pyrazoline and Pyrazoline Derivatives as Anti-Cancer Agents: Synthesis and Biological Activities: A Compressive Review.","authors":"Pushkar Kumar Ray, Ruchi Sharma, Abhishek Kumar","doi":"10.2174/0115680266339816241212081205","DOIUrl":"https://doi.org/10.2174/0115680266339816241212081205","url":null,"abstract":"<p><strong>Background: </strong>A heterocyclic molecule containing five rings, three carbon atoms, two nitrogen atoms, and a single endocyclic bond is called pyrazoline. Because of its intriguing electrical characteristics and potential for dynamic applications, pyrazoline is one type of electron-rich nitrogen carrier that is becoming more and more popular. This study synthesizes pyrazoline derivatives using a variety of techniques to demonstrate a highly biological function.</p><p><strong>Objective: </strong>Pharmaceutical chemistry has found the study of the biological activity of pyrazoline derivatives to be an interesting field. Pyrazolines find utility in numerous multipurpose applications. It has been discussed to examine the current study of patent literature on pyrazoline derivatives (2000-2024) that describes the introduction, general approach, synthesis scheme Structureactivity and relationship, marketed drug, and patents on anticancer activities.</p><p><strong>Conclusion: </strong>A recognized heterocyclic chemical is pyrazolines. Three carbon atoms and two adjacent nitrogen atoms make up the five-membered ring that is pyrazoline. A variety of methods are available to determine its synthesis. Extensive studies have been conducted in this field since it has been found that many pyrazoline derivatives have a crucial biological effect on anticancer activity. The application of pyrazoline as an anticancer agent is a fascinating moiety with a wealth of potential applications for further research by scientists.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946159","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":"Benzimidazole Derivatives in Breast Cancer: Target-Specific Therapeutic Breakthroughs.","authors":"S Mounika, Hemalatha K, Rohit Pal, Gurubasavaraja Swamy Purawarga Matada, Pradan P Jain, Haripriya E, Md Ashadul Sk, Viji M P","doi":"10.2174/0115680266336395241115092048","DOIUrl":"https://doi.org/10.2174/0115680266336395241115092048","url":null,"abstract":"<p><p>Despite ongoing advancements in drug design and developments, breast cancer remains a serious and devastating disease and is ranked as the second most common illness in women. Breast cancer rates have increased significantly during the last 40 years. This necessitates the development of novel treatment techniques. Currently, chemotherapy is the primary mode of treatment for breast cancer; however, its toxicity to normal cells and drug resistance are considered the main obstacles. Researchers are looking for novel anti-breast cancer medication classes to improve cancer therapy efficacy and survival rates. Using non-targeting medicines in a 'one-size-fits-all' strategy can harm healthy cells and may not be effective for all patients. Thus, now, the treatment of breast cancer is exploring targeted-based therapy. The tactics involved in this therapy may improve patient survival rates, but their extended usage can lead to significant side effects and medication resistance. Targeted therapy enables precision medicine by targeting particular oncogenic markers in malignancies. Because of their strong cytotoxicity against several cancer cell types, heterocyclic compounds play an important role in the development of therapeutically effective anticancer drugs. Benzimidazole derivatives have grown in favour of anti-breast cancer medicines in recent years due to their broad biological characteristics and therapeutic applications. This review provides healthcare professionals and researchers with an overview of current breakthroughs (2019-2024) in benzimidazole derivatives as breast cancer-targeted therapy, based on the perspectives of leading experts. We have illuminated the diverse and evolving landscape of hybridized benzimidazole, along with its biological targets and anti-breast cancer activity. Further, we also have compiled the various ongoing clinical trials of benzimidazole scaffolds as anti-breast cancer agents. A detailed illustration of the structure-activity connection with special emphasis is provided. The effort may help to develop potent, selective, and effective drugs to combat breast cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946152","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":"Synthetic Strategies and Biological Activities of Teixobactin and its Analogs: A Review.","authors":"Dalli Kumari, Govindappa Nagendra","doi":"10.2174/0115680266344835241125074030","DOIUrl":"https://doi.org/10.2174/0115680266344835241125074030","url":null,"abstract":"<p><p>Antibiotics are a revolutionary discovery in modern medicine, enabling the successful treatment of bacterial infections that were once untreatable and deadly. Teixobactin, a \"head-toside- chain\" cyclodepsipeptide, shows great promise as a lead compound for developing new antibiotics to deal with multi-drug-resistant bacterial infections. The unique pharmacological profile and intriguing structural characteristics of teixobactin, including its unusual amino acid residues (three D-amino acids and L-allo-enduracididine), have drawn the attention of multiple research groups seeking to create new antibiotics with innovative mechanisms. This review explores recent developments in the chemical structure of teixobactin, its biological role in cells, its biosynthetic production pathway, and how it disrupts bacteria (mode of action). Along with the structureactivity relationship (SAR) studies, this review also covers various synthetic approaches used to create teixobactin and its analogs. Finally, some observations regarding emerging patterns during the synthesis of unique analogs of teixobactin, as well as suggestions for further research and developments, are discussed.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946161","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 Comprehensive Review of mRNA-based Vaccines for COVID-19, A New Era in Pharmaceuticals: Unspecified and Unknown Aspects, Effects and Challenges.","authors":"Pegah Vosoughi, Seyed Morteza Naghib, Mehdi Rahmanian, M R Mozafari","doi":"10.2174/0115680266325847241121034100","DOIUrl":"https://doi.org/10.2174/0115680266325847241121034100","url":null,"abstract":"<p><p>Ongoing research and development efforts are currently focused on creating COVID-19 vaccines using a variety of platforms. Among these, mRNA technology stands out as a cuttingedge method for vaccine development. There is a growing public awareness of mRNA and its potential in vaccine development. Despite being relatively recent, extensive scientific research has been dedicated to vaccines for a considerable period. mRNA vaccines are created by synthesizing the spike protein from a DNA template. This review delves into the various aspects of these vaccines and thoroughly explores the intricacies of COVID-19 vaccinations. It is essential to choose a reliable, efficient, and widely accessible vaccine to combat COVID-19. However, due to the possibility of virus mutations, developing a dependable and safe vaccine is crucial to prepare for future outbreaks of SARS-CoV-2 variants. Meanwhile, concerns remain regarding the potential risks associated with these vaccines.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946124","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 Review on Medicinal Approaches of Novel Imatinib Derivatives.","authors":"Suresh Kumar, Gaurav Agarwal, Kavita Sangwan","doi":"10.2174/0115680266332163241127114029","DOIUrl":"https://doi.org/10.2174/0115680266332163241127114029","url":null,"abstract":"<p><p>Phenyl amino pyrimidine attracts researchers due to its versatile scaffold and medicinal significance. This significant moiety present in the Imatinib contributed to medicinal chemistry. In this manuscript, we reviewed various derivatives of Imatinib containing 2-phenylaminopyrimidine, which has a variety of roles, especially in the anti-cancer category. This manuscript aims to prepare a scientific report that underscores the novel Imatinib derivatives in the field of chemistry for various activities such as anti-cancer, anti-microbial, and miscellaneous focused on cardiovascular, anti-platelets, and anti-parasitic, etc. Finally, this manuscript may attract researchers for new structure design, and the development of novel phenyl amino pyrimidine scaffolds that are more active and less harmful. We propose a compilation and analysis of around 100 Imatinib derivatives having main chromatophores, such as phenylaminopyrimidine. A large number of researchers are interested in Imatnib-based analogs as they have wide biological potential in the largely developing chemical world of the heterocyclic moiety. The phenylamino pyrimidine moiety became an important moiety for researchers to discover combinational libraries and implement the efforts in search of the lead entities. Phenylaminopyrimidine has been manifesting to be an effective moiety in the current respective disease scenario. It has been discovered that phenylaminopyrimidine and its derivatives have an extensive spectrum of pharmacological potential with numerous applications in academic interest, in the pharmaceutical industry, medicinal chemistry, etc. Imatinib containing phenylaminopyrimidine and its novel synthetic derivatives are a prominent heterocyclic compound class with intriguing use in medicinal chemistry. Thus, in brief, attention should be given to other chemical approaches for synthesizing novel compounds containing phenylaminopyrimidine moiety, hence potentiating their efficacy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946149","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}