Mini reviews in medicinal chemistry最新文献

{"title":"The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.","authors":"Ziyan Zhang, Zhuowei Wang, Hong Fan, Jiayi Li, Jiaqi Ding, Gang Zhou, Chengfu Yuan","doi":"10.2174/0113895575285276240324080234","DOIUrl":"https://doi.org/10.2174/0113895575285276240324080234","url":null,"abstract":": Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"2014 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Perspectives in the Development of Novel EGFR Inhibitors for the Treatment of NSCLC","authors":"Rahul Makhija, Anushka Sharma, Rahul Dubey, Vivek Asati","doi":"10.2174/0113895575296174240323172754","DOIUrl":"https://doi.org/10.2174/0113895575296174240323172754","url":null,"abstract":": Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects about 2.2 million people across the globe, according to International Agency for Research on Cancer (IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific and responsible for undesirable adverse effects. Moreover, to solve this problem search for newer EGFR inhibitors is the utmost need for the treatment and/or management of increasing lung cancer burden. The discovery of therapeutic agents that inhibit the specific target in tumorous cells, such as EGFR, is one of the successful strategies in treating many cancer therapies, including lung cancer. The exhaustive literature survey (2018-2023) has shown the importance of medicinally privileged pyrimidine derivatives together, fused and/or clubbed with other heterocyclic rings to design and develop novel EGFR inhibitors. Pyrimidine derivatives substituted with phenylamine, indole, pyrrole, piperazine, pyrazole, thiophene, pyridine and quinazoline derivatives substituted with phenylamine, pyrimidine, morpholine, pyrrole, dioxane, acrylamide, indole, pyridine, furan, pyrimidine, pyrazole etc. are privileged heterocyclic rings shown promising activity by inhibiting EGFR and TKIs. The present review summarizes the structure-activity relationship (SAR) and enzyme inhibitory activity, including IC50 values, percentage inhibition, and kinetic studies of potential compounds from various literature. The review also includes various aspects of molecular docking studies with compounds under clinical trials and patents filed on pyrimidine-based EGFR inhibitors in treating non-small cell lung cancer. The present review may benefit the medicinal chemist for developing novel compounds such as EGFR inhibitors.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"38 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mini-Review on Vitamin D in Pediatric Population and its Role in Respiratory and Atopic Disorders","authors":"Cristiana Indolfi, Angela Klain, Giulio Dinardo, Fabio Decimo, Maria Maddalena Marrapodi, Amelia Licari, Michele Miraglia del Giudice","doi":"10.2174/0113895575284873240212045431","DOIUrl":"https://doi.org/10.2174/0113895575284873240212045431","url":null,"abstract":": In recent years, our comprehension of the function of vitamin D has significantly evolved. The ubiquitous presence of the vitamin D receptor (Vitamin D Receptor- VDR) in the body has led to its redefinition from a steroidal hormone primarily involved in skeletal functions to a hormone with pleiotropic effects, exerting its influence on the circulatory, nervous, and immune systems. This has prompted investigations into its potential use in preventing and treating chronic metabolic disorders, cardiovascular diseases, infections, and allergic and autoimmune diseases. This comprehensive review explores the various aspects of vitamin D, including its sources, synthesis, functions, and its impact on different physiological systems. It delves into the epidemiology of vitamin D deficiency, highlighting its occurrence among various age demographics and geographic regions. The impact of vitamin D on the immune system is also explored, elucidating its immunomodulatory and anti-inflammatory properties, particularly in the context of respiratory infections. The review discusses emerging evidence concerning the potential advantages of vitamin D in respiratory diseases, pediatric asthma and atopic dermatitis. It also addresses vitamin D supplementation recommendations for various pediatric populations, including term and preterm infants. The growing concern regarding the global health impacts of insufficient vitamin D levels necessitates further research to bridge gaps in knowledge, particularly in enhancing screening, prevention, and approaches to address vitamin D deficiency from birth onwards. In summary, this comprehensive overview underscores the vital role of vitamin D, highlighting the significance of understanding its multifaceted functions and the need for tailored supplementation strategies, especially in vulnerable populations.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"149 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Search for Antidotes Against Ricin","authors":"Fernanda Diniz Botelho, Tanos Celmar Costa Franca, Steven R. LaPlante","doi":"10.2174/0113895575270509231121060105","DOIUrl":"https://doi.org/10.2174/0113895575270509231121060105","url":null,"abstract":"The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available. However, some progress has been made, and the development of an effective treatment may be on the horizon. To provide an updated overview of this issue, we have conducted a comprehensive review of the literature on the current state of research in the fight against ricin. This mini-review is based on the reported research and aims to address the challenges faced by researchers, as well as highlight the most successful cases achieved thus far. Our goal is to encourage the scientific community to continue their efforts in this critical search.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"10 3 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139553768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levothyroxine and Non-alcoholic Fatty Liver Disease: A Mini Review.","authors":"Partha Sarathi Singha, Suvendu Ghosh, Debosree Ghosh","doi":"10.2174/1389557523666230314113543","DOIUrl":"10.2174/1389557523666230314113543","url":null,"abstract":"<p><p>Levothyroxine or l-thyroxine is artificially manufactured thyroxine, which is used as a drug to treat underactive thyroid conditions in humans. The drug, levothyroxine, is consumed daily in a prescribed dose to replace the missing thyroid hormone thyroxine in an individual with an underactive thyroid, and it helps to maintain normal physiological conditions. Though it is a life-maintaining drug, it replaces the missing thyroid hormone and performs the necessary daily metabolic functions in our body. Like all other allopathic drugs, it comes with certain side effects, which include joint pain, cramps in muscle, weight gain/loss, hair loss, <i>etc</i>. The thyroid hormone, thyroxine, is known to mobilize fat in our body, including the ones from the hepatic system. An underactive thyroid may cause an accumulation of fat in the liver, leading to a fatty liver, which is clinically termed Non-Alcoholic Fatty Liver Disease (NAFLD). The correlation between hypothyroidism and NAFLD is now well-studied and recognized. As levothyroxine performs the functions of the missing thyroxine, it is anticipated, based on certain preliminary studies, that the drug helps to mobilize hepatic fat and thus may have a crucial role in mitigating the condition of NAFDL.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"128-138"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9482129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.","authors":"Mohammad Owais, Arun Kumar, Syed Misbahul Hasan, Kuldeep Singh, Iqbal Azad, Arshad Hussain, Suvaiv, Mohd Akil","doi":"10.2174/0113895575281039231218112953","DOIUrl":"10.2174/0113895575281039231218112953","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like &lt;i&gt;Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae&lt;/i&gt;, and others.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC&lt;sub&gt;50&lt;/sub&gt; values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-wi","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"1238-1251"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of Accelerated Molecular Dynamics Simulations in Predictions of Binding Kinetic Parameters.","authors":"Jianzhong Chen, Wei Wang, Haibo Sun, Weikai He","doi":"10.2174/0113895575252165231122095555","DOIUrl":"10.2174/0113895575252165231122095555","url":null,"abstract":"<p><p>Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"1323-1333"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Ferroptosis: A Novel Strategy for the Treatment of Atherosclerosis.","authors":"Yifan Zhang, Chengshi Jiang, Ning Meng","doi":"10.2174/0113895575273164231130070920","DOIUrl":"10.2174/0113895575273164231130070920","url":null,"abstract":"<p><p>Since ferroptosis was reported in 2012, its application prospects in various diseases have been widely considered, initially as a treatment direction for tumors. Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis. The primary mechanism is to affect the occurrence and development of atherosclerosis through intracellular iron homeostasis, ROS and lipid peroxide production and metabolism, and a variety of intracellular signaling pathways. Inhibition of ferroptosis is effective in inhibiting the development of atherosclerosis, and it can bring a new direction for treating atherosclerosis. In this review, we discuss the mechanism of ferroptosis and focus on the relationship between ferroptosis and atherosclerosis, summarize the different types of ferroptosis inhibitors that have been widely studied, and discuss some issues worthy of attention in the treatment of atherosclerosis by targeting ferroptosis.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"1262-1276"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting STAT3 Enzyme for Cancer Treatment.","authors":"Sowmiya Arun, Praveen Kumar Patel, Kaviarasan Lakshmanan, Kalirajan Rajangopal, Gomathi Swaminathan, Gowramma Byran","doi":"10.2174/0113895575254012231024062619","DOIUrl":"10.2174/0113895575254012231024062619","url":null,"abstract":"<p><p>A category of cytoplasmic transcription factors called STATs mediates intracellular signaling, which is frequently generated at receptors on cell surfaces and subsequently sent to the nucleus. STAT3 is a member of a responsible for a variety of human tumor forms, including lymphomas, hematological malignancies, leukemias, multiple myeloma and several solid tumor types. Numerous investigations have demonstrated constitutive STAT3 activation lead to cancer development such as breast, head and neck, lung, colorectal, ovarian, gastric, hepatocellular, and prostate cancers. It's possible to get a hold of the book here. Tumor cells undergo apoptosis when STAT3 activation is suppressed. This review highlights the STAT3 activation and inhibition which can be used for further studies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"1252-1261"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application of MD Simulation to Lead Identification, Vaccine Design, and Structural Studies in Combat against Leishmaniasis - A Review.","authors":"Saravanan Vijayakumar, Lukkani Laxman Kumar, Subhomoi Borkotoky, Ayaluru Murali","doi":"10.2174/1389557523666230901105231","DOIUrl":"10.2174/1389557523666230901105231","url":null,"abstract":"<p><p>Drug discovery, vaccine design, and protein interaction studies are rapidly moving toward the routine use of molecular dynamics simulations (MDS) and related methods. As a result of MDS, it is possible to gain insights into the dynamics and function of identified drug targets, antibody-antigen interactions, potential vaccine candidates, intrinsically disordered proteins, and essential proteins. The MDS appears to be used in all possible ways in combating diseases such as cancer, however, it has not been well documented as to how effectively it is applied to infectious diseases such as Leishmaniasis. As a result, this review aims to survey the application of MDS in combating leishmaniasis. We have systematically collected articles that illustrate the implementation of MDS in drug discovery, vaccine development, and structural studies related to Leishmaniasis. Of all the articles reviewed, we identified that only a limited number of studies focused on the development of vaccines against Leishmaniasis through MDS. Also, the PCA and FEL studies were not carried out in most of the studies. These two were globally accepted utilities to understand the conformational changes and hence it is recommended that this analysis should be taken up in similar approaches in the future.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":"1089-1111"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}