Medicinal Chemistry最新文献

{"title":"Recent Advances in Molecular Docking Techniques: Transforming Perspectives in Distinct Drug Targeting and Drug Discovery Approaches.","authors":"Rashid M Ansari, Radhika N Mundke, Yogeeta O Agrawal, Sameer N Goyal, Kartik T Nakhate, Sumit S Rathod","doi":"10.2174/0115734064384472250716144736","DOIUrl":"https://doi.org/10.2174/0115734064384472250716144736","url":null,"abstract":"<p><strong>Introduction: </strong>Drug targeting and drug discovery methodologies are advancing rapidly due to recent developments in molecular docking techniques. Molecular docking forecasts the interactions between a small molecule, such as a potential medicine, and a target protein or receptor.</p><p><strong>Objectives: </strong>This comprehensive review focuses on significant advances in molecular docking algorithms such as Vina, Glide, and AutoDock, including their enhanced accuracy and efficiency in predicting drug-target interactions. It also examines how novel features, such as fragment-based docking, covalent docking, and virtual screening, have expanded the significance of docking in modern pharmaceutical research.</p><p><strong>Methods: </strong>The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as Molecular Docking, Lead-Optimization, Protein Flexibility, Fragment-Based Docking, Covalent Docking, and Virtual Screening.</p><p><strong>Results: </strong>This present state-of-the-art review highlights recent advances in various docking methodologies and their significant applications in drug discovery, while also discussing the scoring functions of some well-established studies. Furthermore, by predicting the interactions between putative medications and protein residues involved in the creation of covalent bonds, covalent docking provides new opportunities for targeting difficult drug-resistant mutations. The efficiency and precision of these simulations have been increased by improved sampling techniques and sophisticated algorithms, enabling the investigation of conformational changes and protein flexibility throughout the drug-binding process.</p><p><strong>Conclusion: </strong>These approaches may hasten the course of emerging new remedies, increase the precision of hit-finding, and make it easier to find cutting-edge treatments for a variety of diseases. Molecular docking alone is insufficient to ensure the safety and efficacy of a pharmacological agent for commercialization. While it predicts binding affinity and interaction, it does not account for pharmacokinetics, toxicity, off-target effects, or in vivo behavior. Therefore, experimental validation through MD simulation, ADMET, in vitro, in vivo, and clinical studies is essential.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690718","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 Search for New Amidrazone Derivatives Containing 4-Oxybut-2-enoic Acid Moiety as Antibacterial Agents.","authors":"Renata Paprocka, Monika Przybysz, Kamila Pośpieszyńska, Ashley Chepkoech, Dominika Jagleniec, Antoni Godlewski, Karolina Korczak, Małgorzata Wiese-Szadkowska, Jolanta Kutkowska","doi":"10.2174/0115734064396576250706091217","DOIUrl":"https://doi.org/10.2174/0115734064396576250706091217","url":null,"abstract":"<p><strong>Introduction: </strong>Bacterial diseases pose a significant challenge to modern medicine due to the rapid development of resistance by bacterial strains and the global migration of people, which facilitates the transmission of these diseases. Therefore, there is a need to develop new strategies to combat microorganisms and newer substances that could be used as antibiotics.</p><p><strong>Methods: </strong>Six new derivatives, <b>2a-2f</b>, containing a 4-oxybut-2-enoic acid moiety, were obtained by reacting amidrazones with maleic anhydride. The antimicrobial potency of compounds <b>2a-2f</b> was studied using the microdilution method against the following bacterial strains: <i>Escherichia coli, Yersinia enterocolitica, Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Gordonia rubripertincta, Mycobacterium smegmatis</i>, and the fungal strain <i>Candida albicans</i>. Their antiproliferative activity was tested in cultures of human peripheral blood mononuclear cells stimulated with phytohemagglutinin. The bioavailability parameters of new compounds were predicted using Molinspiration software.</p><p><strong>Results: </strong>Derivatives <b>2a-2c</b> showed the strongest antibacterial activity, especially against <i>Yersinia enterocolitica</i> and <i>Micrococcus luteus</i>. Compounds <b>2d-2f</b> inhibited the growth of <i>Gordonia rubripertincta</i>. Compounds <b>2a-2f</b> exhibited low antiproliferative activity towards human peripheral blood mononuclear cells. However, it is necessary to evaluate whether all compounds are well absorbed after oral administration.</p><p><strong>Discussion: </strong>The most promising antibacterial activity was demonstrated by derivatives possessing a 2-pyridyl substituent at the R1 position (<b>2a-2c</b>) or a phenyl ring at the R² position (2a, 2f).</p><p><strong>Conclusion: </strong>Compound <b>2a</b> demonstrated the highest antibacterial activity and selectivity in inhibiting the growth of <i>Y. enterocolitica</i>. Additionally, it exhibited low toxicity to human lymphocytes and demonstrated favorable bioavailability parameters. Therefore, its structure can be used as a starting point for designing new antimicrobials, such as targeted therapies for yersiniosis, beyond traditional antibiotics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649868","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":"Antioxidant and Cytotoxic Activity of the Aporphine Alkaloid (Boldine) Against DMH-induced Colorectal Carcinogenesis in Wistar Rats: An <i>In silico, In vitro</i>, and <i>In vivo</i> study.","authors":"Monu Kumar Kashyap, Akash Ved, Pranay Wal, Akhand Pratap Singh","doi":"10.2174/0115734064358287250613065507","DOIUrl":"https://doi.org/10.2174/0115734064358287250613065507","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this study is to investigate the role of the aporphine alkaloid boldine as a potential inhibitor of specific protein targets involved in colorectal cancer, using &lt;i&gt;in silico&lt;/i&gt; docking and molecular dynamics simulation studies, and to evaluate its therapeutic potential in modulating the pathological progression of colorectal cancer. In this study, we evaluated the antioxidant and cytotoxic effects of boldine using &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; methods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The 2-dimensional structure of boldine was retrieved from the PubChem database. Its interactions with colorectal cancer target proteins were analyzed using structures obtained from the RCSB Protein Data Bank (https://www.rcsb.org/), which provides the crystal structures of tubulin (PDB ID: 1Z2B), human NF- κB (1A3Q), human interleukin-2 (1M47), and EGFR-kinase. Molecular docking was then performed using Schrödinger software. Molecular docking and molecular dynamics (MD) simulations were conducted to evaluate Boldine's binding affinity and stability with colorectal cancer protein targets. On the Growmac platform, we performed the molecular simulation, and the simulation was only done with the highest docking score. Additionally, molecular dynamics was performed for 100 ns. Boldine was added to the colorectal cancer cell line (HCT116) at different doses, and the cytotoxic effects of the treatment were evaluated using cell viability assays. Furthermore, Boldine's capacity to scavenge reactive oxygen species (ROS) and modify the oxidative stress assay &lt;i&gt;in vitro&lt;/i&gt; was used to assess its antioxidant capability. Boldine's in vivo anticancer effectiveness was examined using DMH-induced colorectal cancer in Wistar Rats. After Boldine was administered (100mg/Kg), Tumour progression, histological alteration, and oxidative stress markers were evaluated. The study aimed to ascertain how boldine affects tumor growth in DMH-inducedDMH colorectal carcinogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Molecular docking revealed favorable binding interactions between boldine and key targets implicated in colorectal cancer. The &lt;i&gt;in silico&lt;/i&gt; data supported the hypothesis that boldine modulates essential pathways associated with cancer development. Boldine exhibited a dose-dependent reduction in colorectal cancer cell viability, indicating potential cytotoxic effects. Furthermore, boldine demonstrated antioxidant properties by effectively scavenging reactive oxygen species (ROS) and modulating oxidative stress markers in vitro. In animal models, boldine administration resulted in a significant reduction in tumor growth. Histopathological examination revealed favorable changes in tumor morphology. Additionally, boldine demonstrated antioxidant effects in vivo by modulating oxidative stress markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;According to this extensive study performed &lt;i&gt;in silico&lt;/i&gt;, &lt;i&gt;in vitro&lt;/i&gt;, and &lt;i&gt;in vivo&lt;/i&gt;, bol","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575787","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":"Promising Flavone Derivatives as Anticancer Agents.","authors":"Vishakha A Patil, Kalyani R Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar","doi":"10.2174/0115734064384513250624043626","DOIUrl":"https://doi.org/10.2174/0115734064384513250624043626","url":null,"abstract":"<p><p><p> Currently, the main focus of anticancer drug development and research is to develop anticancer treatment strategies that are both less harmful and more effective. Flavones, a subclass of flavonoids, have shown great promise in the advancement of anticancer drugs because of their strong bioactive properties. Fruits, vegetables, and medicinal plants are abundant sources of these naturally occurring compounds, which have a variety of biological activities such as anti-inflammatory, anti-cancer, and antioxidant properties. Flavones and their derivatives have attracted a lot of attention recently because of their potential to modify significant molecular pathways that are involved in the growth, apoptosis, angiogenesis, and metastasis of cancer cells. The objective of this review is to present a thorough analysis of the chemical makeup of flavone as an anticancer agent. By altering the flavone scaffold's structure, there are beneficial chances to improve its therapeutic qualities, such as its potency, selectivity, and pharmacokinetics. The structural alterations of flavone derivatives that improve their anticancer potency and selectivity are highlighted. Most noteworthy, flavones offer a promising framework for the creation of new anticancer medications, and further research into them may help create more potent and focused cancer treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560516","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":"Exploring the Cholinesterase Inhibitory Potential of Azines Bearing a 4,4-bisdimethylaminobenzophenone Scaffold: An Experimental and Computational Approach.","authors":"Ghulam Ahad, Aftab Alam, Ahmed A Elhenawy, Imtiaz Ahmad, Fayaz Ur Rahman, Munir Ur Rehman, Abid Ali, Abdullah F AlAsmari, Fawaz Alasmari, Momin Khan","doi":"10.2174/0115734064375363250620173232","DOIUrl":"https://doi.org/10.2174/0115734064375363250620173232","url":null,"abstract":"<p><strong>Background: </strong>Acetyl and butyrylcholinesterase are significant enzymes involved in neurological diseases, and the development of more effective inhibitors is crucial for beneficial interference.</p><p><strong>Objective: </strong>To evaluate the cholinesterase inhibition effect of the synthetic bis-Schiff base compounds and discover the electronic properties as well as binding affinities through computational studies.</p><p><strong>Methods: </strong>The compounds were synthesized and screened against acetyl and butyrylcholinesterase inhibitory activities in-vitro, while DFT analysis and molecular docking studies were performed for the product compounds.</p><p><strong>Results: </strong>Seven compounds, including <b>2a, 2b, 2e, 2c, 2d, 2i</b>, and <b>2j</b>, exhibited excellent AChE activity, while nine compounds showed potent BChE inhibition compared to galantamine (IC50 = 156.4 ± 1.13 μM). Furthermore, the recent study on molecules 2a-e has provided valuable insights into their mechanism of action as inhibitors of the enzyme ChE, which is crucial for understanding how to regulate this enzyme's activity. Through the use of Time-Dependent Density Functional Theory (TD-DFT), the electronic characteristics of these molecules were meticulously examined, revealing that the Highest Occupied Molecular Orbitals (HOMO) are extensively delocalized across the molecular frameworks of the most active <b>2a-e</b> compounds. This suggests a significant degree of electron delocalization, which is often associated with chemical reactivity and stability. In comparison to standard galantamine, these compounds demonstrate a lower electrophilicity index, which is indicative of their increased biological efficacy and lower toxicity.</p><p><strong>Conclusion: </strong>These derivatives showed excellent AChE and BChE activities with favorable electronic properties and superior binding affinities, highlighting their potential as effective inhibitors as therapeutic agents.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540808","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":"Optimized Strategies for the Synthesis and Structure-Activity Relationship of Imidazole as an Antiepileptic Drug.","authors":"Saloni Mangal, Salahuddin, Avijit Mazumder, Rajnish Kumar, Sapna Rani, Vimal Datt, Mohamed Jawed Ahsan, Mohammad Shahar Yar","doi":"10.2174/0115734064377779250529172030","DOIUrl":"https://doi.org/10.2174/0115734064377779250529172030","url":null,"abstract":"<p><p>Imidazole is believed to be a highly multifunctional compound in the medicinal and biological sectors. This literature focuses on information about the synthesis and anticonvulsant activity presented by the imidazole nucleus. Epilepsy is a chronic brain disorder including multiple seizures and brain cell abnormalities. Due to its old and less effective treatment, with the increase in the number of patients suffering from epilepsy, researchers need to concentrate on the emergence of finding new treatments for epilepsy. Imidazole-containing analogs are found to be significant in the field of medicinal chemistry and the treatment for epilepsy. These studies prompted us to synthesize and provide insights into developing new imidazole-bearing antiepileptic drugs.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285403","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":"Potential Inhibitors of SARS-CoV-2 Developed through Machine Learning, Molecular Docking, and MD Simulation.","authors":"Arshiya Khan, Anushka Bhrdwaj, Khushboo Sharma, Ravali Arugonda, Navpreet Kaur, Rinku Chaudhary, Uzma Shaheen, Umesh Panwar, V Natchimuthu, Abhishek Kumar, Taniya Dey, Aravind Panicker, Leena Prajapati, Nhattuketty Krishnan Shainy, Muhammed Marunnan Sahila, Francisco Jaime Bezerra Mendonça Junior, Tajamul Hussain, Salman Alrokayan, Anuraj Nayarisseri","doi":"10.2174/0115734064370188250527043536","DOIUrl":"https://doi.org/10.2174/0115734064370188250527043536","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The advent of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19) pandemic, has impacted physical and mental health worldwide. The lack of effective antiviral drugs necessitates a robust therapeutic approach to develop anti-SARS-CoV-2 drugs. Various investigations have recognized ACE2 as the primary receptor of SARS-CoV-2, and this amalgamation of ACE2 with the spike protein of the coronavirus is paramount for viral entry into the host cells and inducing infection. Consequently, restricting the virus's accessibility to ACE2 offers an alternative therapeutic approach to averting this illness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The study aimed to identify potent inhibitors with enhanced affinity for the ACE2 protein and validate their stability and efficacy against established inhibitors via molecular docking, machine learning, and MD simulations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;202 ACE2 inhibitors (PDB ID and 6LZG), comprising repurposed antiviral compounds and specific ACE2 inhibitors, were selected for molecular docking. The two most effective compounds obtained from docking were further analyzed using machine learning to identify potential compounds with enhanced ACE2-binding affinity. To refine the dataset, molecular decoys were generated through the Database of Useful Decoys: Enhanced (DUD-E) server, and Singular Value Decomposition (SVD) was applied for data preprocessing. The Tree-based Pipeline Optimization Tool (TPOT) was then utilized to optimize the machine learning pipeline. The most promising ML-predicted compounds were re-evaluated through docking and subjected to Molecular Dynamics (MD) simulations to evaluate their structural stability and interactions with ACE2. Finally, these compounds were evaluated against the top two pre-established inhibitors using various computational tools.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The two best pre-established inhibitors were identified as Birinapant and Elbasvir, while the best machine-learning-predicted compounds were PubChem ID: 23658468 and PubChem ID: 117637105. Pharmacophore studies were conducted on the most effective machine-learning-predicted compounds, followed by a comparative ADME/T analysis between the best ML-screened and pre-established inhibitors. The results indicated that the top ML compound (PubChem ID: 23658468) demonstrated favorable BBB permeability and a high HIA index, highlighting its potential for therapeutic applications. The ML-screened ligand demonstrated structural stability with an RMSD (0.24 nm) and greater global stability (Rg: 2.08 nm) than Birinapant. Hydrogen bonding interactions further validated their strong binding affinity. MM/PBSA analysis confirmed the ML-screened compound's stronger binding affinity, with a binding free energy of - 132.90 kcal/mol, indicating enhanced stability in complex formation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The results emp","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216279","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":"Synthesis, Characterization, and Pharmacological Evaluation of Zn₄O(BDC)₃: Anticancer, Antidiabetic, and Drug Delivery Potential.","authors":"Sabir Khan, Muhammad Fazal Hameed, Imran Zafar, Rubina Bibi, Mohamed Mohany, Sadia Nazir, Mohammad Amjad Kamal, Muhammad Shafiq","doi":"10.2174/0115734064362203250222050726","DOIUrl":"https://doi.org/10.2174/0115734064362203250222050726","url":null,"abstract":"<p><strong>Introduction: </strong>This study presents a comprehensive exploration of the biomedical potential of the synthesized metal-organic framework Zn₄O(BDC)₃, focusing on its applications in cancer and diabetes treatment and its advanced drug delivery capabilities.</p><p><strong>Methods: </strong>The structural and physicochemical properties of Zn₄O(BDC)₃ were characterized using FTIR, TGA, ¹H NMR, PXRD, and elemental analysis, revealing its exceptional stability and coordination properties. Molecular docking, molecular dynamics simulations (100 ns), and MM-GBSA calculations were performed to assess binding affinities and stability.</p><p><strong>Results: </strong>The interactions of Zn₄O(BDC)₃ with salmon sperm DNA (SSDNA) and bovine serum albumin (BSA) demonstrated significant anticancer potential, evidenced by binding constant values of 6.0 × 10⁶M^-1 and Gibbs free energy changes of -17.93 and -19.61 kcal/mol, respectively, highlighting its ability to suppress tumor cell proliferation. With doxorubicin (DOX) loading and reloading efficiencies of 88% and 87.5%, Zn₄O(BDC)₃ exhibited superior drug delivery capabilities. The anti-diabetic potential was validated by the formation of human insulin (HI) hexamers with ΔG values of 0.8 ± 0.1 and a significant decrease in absorption intensity (5.8 to 0.05 at 250 nm). Molecular docking studies revealed moderate to high binding affinities (-10.0 to -5.3 kcal/mol) with biomolecular targets, supported by molecular dynamics simulations over 100 ns and MM-GBSA calculations indicating robust stability (ΔG = -33.31 kcal/mol).</p><p><strong>Conclusion: </strong>These <i>in-silico</i> and <i>in-vitro</i> analyses underscore the significant pharmacological promise of Zn₄O(BDC)₃ as a multifunctional agent for anticancer, antidiabetic, and drug delivery applications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009281","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":"Reducing Cabozantinib Toxicity in Renal Cell Carcinoma Treatment through Structural Modifications.","authors":"Jiaxiang Guo, Xiaotao Yin, Yongliang Lu, Yu Yang","doi":"10.2174/0115734064374511250411104320","DOIUrl":"10.2174/0115734064374511250411104320","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cabozantinib, a Tyrosine Kinase Inhibitor (TKI), is widely used in Renal Cell Carcinoma (RCC) therapy but often causes serious side effects such as myelosuppression, immunosuppression, and angiopathy. This study aims to identify key protein targets responsible for the therapeutic efficacy and adverse reactions of cabozantinib and to explore structural modifications to reduce toxicity while preserving efficacy.</p><p><strong>Methods: </strong>A non-randomized computational approach was employed, screening 400 potential protein targets using SwissTargetPrediction and ChemBL databases. Molecular docking and Structure-Activity Relationship (SAR) analysis were performed to assess interactions between cabozantinib and identified targets, focusing on structural elements contributing to toxicity.</p><p><strong>Results: </strong>Three primary proteins were identified as responsible for the anti-tumor effects of cabozantinib, while three others were linked to its side effects. Docking analysis revealed that the methoxyphenyl group in cabozantinib formed undesirable hydrogen bonds with toxicity-related proteins. Modulating these off-target interactions by minimizing hydrogen bonding in this region could significantly reduce adverse effects.</p><p><strong>Conclusion: </strong>These findings provide structural insights into cabozantinib's dual effects and suggest optimization strategies for TKI design, offering a pathway toward safer and more effective RCC treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyridine Derivatives: A Comprehensive Review of Their Potential as Anti-Diabetic Agents.","authors":"Deepak Dua, Prakash Kumar, Riya Anand, Salvi Sood, Gurdeep Singh","doi":"10.2174/0115734064342827241230053148","DOIUrl":"https://doi.org/10.2174/0115734064342827241230053148","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus and obesity are two of the most frequent health conditions in the world, prompting medical researchers to seek novel effective treatments. According to World Health Organization (WHO) regulations and several research studies, diabetes is regarded as a significant and leading health concern worldwide. The search for efficient and safe antidiabetic drugs has led to the study of pyridine derivatives, a family of molecules with a wide range of pharmacological characteristics. Pyridines are important heterocyclic chemicals renowned for their various pharmacological properties.</p><p><strong>Methods: </strong>Materials were compiled using the three databases of ScienceDirect, PubMed, and Google Scholar. For this study, only English-language publications have been evaluated based on their titles, abstracts, and full texts using keywords like diabetes, pyridine Derivatives, α- glucosidase inhibitors, and α-amylase inhibitors.</p><p><strong>Results: </strong>Pyridine and its derivatives have received a lot of attention due to their wide range of potential uses in medicinal chemistry and pharmacology. Structural alterations and optimization efforts have resulted in higher effectiveness, selectivity, and safety characteristics. These discoveries highlight the importance of pyridine analogues as a novel class of therapeutic agents for diabetes management.</p><p><strong>Conclusion: </strong>The review highlights the significance of pyridine analogues in the development of antidiabetic treatments, opening new avenues for developing drugs and clinical use. The ongoing advancements in the discovery of pyridine derivatives underscore their potential as prospective agents in diabetic treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047234","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}