Future medicinal chemistry最新文献

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Design, synthesis, in silico, anticancer evaluations of N-acylhydrazone derivatives as STAT3 inhibitors. n -酰基腙衍生物作为STAT3抑制剂的设计、合成和抗癌评价。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-14 DOI: 10.1080/17568919.2025.2527604
Vivek Panwar, Yajat Rohila, Aishwarya Singh, Meenakshi, Bhavana Singh, Manoj K Gupta, Manoj Garg, Deepak Kumar
{"title":"Design, synthesis, <i>in silico</i>, anticancer evaluations of <i>N</i>-acylhydrazone derivatives as STAT3 inhibitors.","authors":"Vivek Panwar, Yajat Rohila, Aishwarya Singh, Meenakshi, Bhavana Singh, Manoj K Gupta, Manoj Garg, Deepak Kumar","doi":"10.1080/17568919.2025.2527604","DOIUrl":"10.1080/17568919.2025.2527604","url":null,"abstract":"<p><strong>Aim: </strong><i>N</i>-acylhydrazone derivatives were synthesized, evaluated in-vitro and further subjected to cell cycle analysis, cell apoptosis, western bloting, and in-silico analysis targeting STAT3.</p><p><strong>Materials and methods: </strong>A series of <i>N</i>-acylhydrazones (<b>5a-5l</b>) were synthesized and evaluated against MIA PaCa-2 cancer cells. 5 h and 5 l were further evaluated against PANC-1, MCF-7 and hTERT-HPNE cells. Additionally, cell cycle analysis, apoptosis, western blotting, docking, in-silico ADMET, molecular dynamics and MM-GBSA were done on <b>5l</b>.</p><p><strong>Results and conclusion: </strong>5 l and 5 h suppressed the growth of MIA PaCa-2 cancer cells and were very less cytotoxic to hTERT-HPNE cells. Additionally, the anticancer efficacy was confirmed against PANC-1 and MCF-7 for <b>5l</b> and <b>5h</b>. Further, <b>5l</b> treatment induced G1/S arrest marked decrease in G2/M and displayed a significant increase in the apoptosis of MIA PaCa-2 cells. 5 l treatment significantly inhibited the phosphorylated level STAT3 and JAK1. In-silico studies confirm the binding affinity and stability and further synthetic modifications and biological investigations can be done to explore the medicinal potential of the derivatives in future.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1509-1519"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625828","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}
引用次数: 0
Design, synthesis, characterization, in silico studies, and in vitro anticancer evaluation of novel 7-methoxyquinolone-substituted triazole hybrids. 新型7-甲氧基喹诺酮取代三唑化合物的设计、合成、表征、硅研究和体外抗癌评价。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-16 DOI: 10.1080/17568919.2025.2533003
Lemıye Allıto, Ferah Comert Onder, Ramazan Demirel, Alper Onder, Özkan Özden, Musa Erdoğan
{"title":"Design, synthesis, characterization, <i>in silico</i> studies, and <i>in vitro</i> anticancer evaluation of novel 7-methoxyquinolone-substituted triazole hybrids.","authors":"Lemıye Allıto, Ferah Comert Onder, Ramazan Demirel, Alper Onder, Özkan Özden, Musa Erdoğan","doi":"10.1080/17568919.2025.2533003","DOIUrl":"10.1080/17568919.2025.2533003","url":null,"abstract":"<p><strong>Aims: </strong>The quinolone scaffold is a crucial member of the heterocyclic compound family in modern medicinal chemistry, exhibiting a broad range of biological activities. Since 4-quinolones are known to interact with significant drug targets, and due to the remarkable pharmacological properties of 1,2,3-triazole compounds, a molecular hybridization approach was used to design novel 7-methoxyquinolone-substituted triazole hybrid conjugates (<b>QN1-QN11</b>).</p><p><strong>Materials and methods: </strong>These hybrid compounds were evaluated to determine their anticancer activities in various breast and colon cancer cell lines, including BT20, MDA-MB-231, MCF7, and HT29. In addition, the apoptotic-like morphological changes in aggressive MDA-MB-231 cells were observed following treatment with the compounds for 48 hours. <i>In silico</i> studies, including molecular docking, molecular dynamics (MD) simulation, and MM/GBSA calculations, were carried out for the synthesized compounds against important cancer drug targets.</p><p><strong>Results: </strong>The highly cytotoxic agents <b>QN10</b> and <b>QN7</b> were identified with IC<sub>50</sub> values of 4.49 ± 0.68 µM and 19.05 ± 1.58 µM in BT20 and HT29 cell lines, respectively. In addition, the morphologically changes were observed on MDA-MB-231 cells.</p><p><strong>Conclusions: </strong>These findings show that the synthesized click products are highly cytotoxic agents in cancer cell lines and may be considered as potential candidates for enzyme inhibition.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1559-1573"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642218","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}
引用次数: 0
Piperidines as dual inhibitors of tyrosinase and pancreatic lipase: in vitro and in silico mechanistic insights. 哌啶作为酪氨酸酶和胰脂肪酶的双重抑制剂:体外和硅机制的见解。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-01 DOI: 10.1080/17568919.2025.2539672
Nafeesa Naeem, Ehsan Ullah Mughal, Bushra Shakoor, Amina Sadiq, Gehan Ahmed Othman, Ercan Bursal, Fuat Yetişsin
{"title":"Piperidines as dual inhibitors of tyrosinase and pancreatic lipase: <i>in vitro</i> and <i>in silico</i> mechanistic insights.","authors":"Nafeesa Naeem, Ehsan Ullah Mughal, Bushra Shakoor, Amina Sadiq, Gehan Ahmed Othman, Ercan Bursal, Fuat Yetişsin","doi":"10.1080/17568919.2025.2539672","DOIUrl":"10.1080/17568919.2025.2539672","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the dual inhibitory potential of a series of piperidine derivatives against tyrosinase and pancreatic lipase. For the first time, these compounds were evaluated concurrently for their inhibitory effects on both enzymes, targeting potential therapeutic applications in hyperpigmentation and obesity-related disorders.</p><p><strong>Materials and methods: </strong>A total of eight piperidine-based compounds were synthesized and assessed for in vitro inhibitory activity against mushroom tyrosinase and pancreatic lipase. The most active derivatives underwent kinetic studies to determine the mode of inhibition using Lineweaver-Burk plots. Structure-activity relationship (SAR) analysis was performed to identify key substituents influencing bioactivity. Furthermore, molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations were conducted to elucidate the binding interactions and electronic properties associated with inhibition.</p><p><strong>Results: </strong>Among the tested compounds, several exhibited significant dual inhibitory activity, with low micromolar IC<sub>50</sub> values against both enzymes. Kinetic analysis revealed competitive inhibition for the lead compound. Docking and MD simulations confirmed stable binding within the active sites of both enzymes, supported by favorable DFT descriptors.</p><p><strong>Conclusions: </strong>These findings reveal, for the first time, that piperidine derivatives possess promising dual inhibitory activity against tyrosinase and pancreatic lipase, supported by both experimental and computational evidence.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1707-1724"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759667","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}
引用次数: 0
Narcotics through time: exploring historical origins, synthetic advances, and clinical progress. 麻醉品穿越时空:探索历史起源、合成进展和临床进展。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-07 DOI: 10.1080/17568919.2025.2527606
Rakesh Chandra Kalita, Shivank Sharma, Suman Samanta, Deepshikha Patle
{"title":"Narcotics through time: exploring historical origins, synthetic advances, and clinical progress.","authors":"Rakesh Chandra Kalita, Shivank Sharma, Suman Samanta, Deepshikha Patle","doi":"10.1080/17568919.2025.2527606","DOIUrl":"10.1080/17568919.2025.2527606","url":null,"abstract":"<p><p>Pain management has remained one of the most critical challenges in clinical medicine over the past several decades, with narcotics continuing to play a central role in controlling moderate to severe pain. Originating from natural sources such as Papaver somniferum, these compounds have evolved significantly from plant-derived alkaloids to highly potent synthetic opioids. However, despite their therapeutic effectiveness, long-standing concerns such as addiction, tolerance, and life-threatening side effects remain major obstacles. This review presents a comprehensive overview of the historical development of narcotics and recent progress in synthetic pain-relief agents. A broad literature survey was conducted, encompassing peer-reviewed articles, clinical trial data, and historical records, complemented by an independent SAR analysis based on the chemical structures of some of the most potent synthetic derivatives reported to date. Key transitions from traditional opioids to synthetic compounds such are explored, alongside novel clinical advancements like Oliceridine (TRV-130), NKTR-181, and Cebranopadol, which demonstrate promising analgesic efficacy with fewer adverse effects. Additionally, recent preclinical studies on synthetic mu-opioid receptor agonists and dual-receptor targeting compounds are discussed for their therapeutic potential. Overall, ongoing research into safer and more effective synthetic opioids offers a hopeful path forward in advancing analgesic therapy.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1587-1599"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575175","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}
引用次数: 0
Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer. 治疗乳腺癌的小分子抑制剂:基于乳腺癌发病机制的药物分析。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-08 DOI: 10.1080/17568919.2025.2542720
Yu Jiang, Zihua Tang, Wenyue Zheng, Xue Xiao
{"title":"Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer.","authors":"Yu Jiang, Zihua Tang, Wenyue Zheng, Xue Xiao","doi":"10.1080/17568919.2025.2542720","DOIUrl":"10.1080/17568919.2025.2542720","url":null,"abstract":"<p><p>Breast cancer (BC) is characterized by the abnormal and rapid growth of breast epithelial cells, driven by various carcinogenic factors. Advances in understanding the signaling pathways and molecular mechanisms involved in BC progression have facilitated the development of small molecule inhibitors for its treatment. Significant progress has been made in creating inhibitors that target the PI3K/AKT/mTOR signaling pathway. Current clinical research focuses on compounds such as GDC-0077 and NVP-BKM120, advancing into phase II/III clinical trials. Preclinical drugs like NVP-CLR457, AZD6482, PF-06843195, and GDC-0326 show promising potential for further optimization and entry into BC clinical trials. This review aims to provide an overview of the clinical and preclinical development of small molecule inhibitors for various molecular subtypes of BC, emphasizing their structural composition, therapeutic outcomes, and mechanisms of action. Additionally, we highlight key targets and pathways involved in BC pathogenesis, offering essential insights for the design of effective therapeutic agents for breast cancer.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1787-1813"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798613","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}
引用次数: 0
Exploring Schiff base bromhexine derivatives: study on synthesis, characterization, biological assays, molecular docking. 希夫碱溴甲辛衍生物的探索:合成、表征、生物检测、分子对接研究。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-12 DOI: 10.1080/17568919.2025.2527619
Zarmeena Yasmeen, Mohsin Abbas Khan, Anum Masood, Toseef Akram, Breena, Mashooq A Bhat, Asim Raza, Javed Ahmed, Saharish Khaliq, Mohamed A Al-Omar, Farhat Ullah
{"title":"Exploring Schiff base bromhexine derivatives: study on synthesis, characterization, biological assays, molecular docking.","authors":"Zarmeena Yasmeen, Mohsin Abbas Khan, Anum Masood, Toseef Akram, Breena, Mashooq A Bhat, Asim Raza, Javed Ahmed, Saharish Khaliq, Mohamed A Al-Omar, Farhat Ullah","doi":"10.1080/17568919.2025.2527619","DOIUrl":"10.1080/17568919.2025.2527619","url":null,"abstract":"<p><strong>Aim: </strong>Schiff bases, owing to their versatile pharmacological and industrial applications, have attracted significant attention in drug design.</p><p><strong>Material and methods: </strong>The newly synthesized Schiff Base derivatives of bromhexine were characterized using spectral techniques, including Infrared (IR), Nuclear Magnetic Resonance (1 H NMR, 13C NMR) analyses. Pharmacokinetic studies via SwissADME web server. Antiviral screening using the hemagglutination inhibition assay identified BM9 as the most potent compound (IC50 = 3.01 ± 1.70). Antioxidant activity was assessed using the DPPH method.</p><p><strong>Results and conclusion: </strong>Molecular docking studies against α-amylase and α-glucosidase revealed strong inhibition scores, with BM6 and BM7 emerging as the most promising candidates. This study concludes that derivatives could serve as lead compounds in the development of novel therapeutic agents.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1547-1558"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617226","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}
引用次数: 0
Recent Advances in dehydroacetic acid-clubbed pyridine conjugates: design, synthesis, characterization, molecular docking investigations and evaluation of anti-cancer efficacy. 脱氢乙酸-棒联吡啶缀合物的研究进展:设计、合成、表征、分子对接研究及抗癌效果评价
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-07-14 DOI: 10.1080/17568919.2025.2533051
Ginna Kumari, Priyanka Rani, Sudeep Dhillon, Mamta Chahal, Swati Rani, Jai Devi, Deepak Kumar Aneja, Mayank Kinger
{"title":"Recent Advances in dehydroacetic acid-clubbed pyridine conjugates: design, synthesis, characterization, molecular docking investigations and evaluation of anti-cancer efficacy.","authors":"Ginna Kumari, Priyanka Rani, Sudeep Dhillon, Mamta Chahal, Swati Rani, Jai Devi, Deepak Kumar Aneja, Mayank Kinger","doi":"10.1080/17568919.2025.2533051","DOIUrl":"10.1080/17568919.2025.2533051","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study was to synthesize novel pyridine conjugates incorporating dehydroacetic acid via the Krohnke reaction and to evaluate their potential as anti-cancer agents. Materials & methods: The Krohnke reaction has previously been reported using acetic acid as the solvent, here we employed ethanol as the reaction medium. The trisubstituted pyridine derivatives were synthesized via a multistep procedure that involved the reaction of pyridinium bromide salts with chalcone derivatives of dehydroacetic acid. The synthesized hybrids were comprehensively characterized using a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform Infrared (FT-IR) spectroscopy, and Mass Spectrometry (MS).</p><p><strong>Results: </strong>These compounds were subjected to in vitro evaluation of their anti-cancer potential against MCF-7 (human breast cancer) and A-549 (human lung cancer) cell lines. The anti-cancer screening results indicate that the synthesized conjugates exhibit potent activity against MCF-7 cells and demonstrate moderate activity against A-549 cell lines.</p><p><strong>Conclusion: </strong>The analysis indicates a binding energy of -9.3 kcal/mol for the 7a derivative, which is closely comparable to that of the standard drug, which exhibits a binding energy of -9.9 kcal/mol.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1575-1586"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625829","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}
引用次数: 0
Evaluation of novel nitrophenol-triazole hybrid molecules: biological screening and computational profiling. 新型硝基苯酚-三唑杂化分子的评价:生物筛选和计算分析。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-07-01 Epub Date: 2025-08-07 DOI: 10.1080/17568919.2025.2539674
Sultan Onur, Mustafa Çeşme, Muhammet Köse, Ferhan Tümer
{"title":"Evaluation of novel nitrophenol-triazole hybrid molecules: biological screening and computational profiling.","authors":"Sultan Onur, Mustafa Çeşme, Muhammet Köse, Ferhan Tümer","doi":"10.1080/17568919.2025.2539674","DOIUrl":"10.1080/17568919.2025.2539674","url":null,"abstract":"<p><p>This study aimed to synthesize novel nitrophenol-triazole hybrid molecules, investigate their biological activities (cholinesterase inhibition, antioxidant, and anticancer effects), and profile them using computational methods (molecular docking, ADMET). Eight new hybrid compounds were successfully synthesized, and the crystal structures of compounds <b>10a and 10g</b> were determined by single-crystal X-ray diffraction analysis. Among the obtained compounds, derivative <b>10e</b> exhibited notable cholinesterase inhibitory activity with high potency and selectivity against acetylcholinesterase (AChE), demonstrating an IC<sub>50</sub> value of 1.56 µM. The compounds displayed promising antioxidant capacity, especially in terms of ABTS radical scavenging activity, with IC<sub>50</sub> values ranging narrowly from 8.01 µg/mL (<b>10a</b>) to 8.52 µg/mL (<b>10d</b>). In anticancer activity evaluations, compound <b>10a</b> showed noteworthy cytotoxicity against the Caco-2 cell line with an IC<sub>50</sub> value of 1.77 µM. In silico ADMET analyses predicted that most compounds adhere to Lipinski's Rule of Five and possess a favorable profile. Molecular docking studies elucidated the binding interactions, revealing binding energies of - 10.9 kcal/mol for compound <b>10e</b> with AChE and - 9.1 kcal/mol for compound <b>10h</b> with BuChE.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1693-1706"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793969","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}
引用次数: 0
Discovery and evaluation of novel pyrrole/thiophene chalcone urea EGFR inhibitors via biological and docking studies. 新型吡咯/噻吩查尔酮脲EGFR抑制剂的发现和评价。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-30 DOI: 10.1080/17568919.2025.2521249
Belma Zengin Kurt, Dilek Öztürk Civelek, Hümeyra Şahin Bektay, Ayşegül Özbilge Ulueren, Yakup Kolcuoğlu, Atilla Akdemir, Ahmet Fatih Şahin, Zeynep Durukan, Fatih Sönmez
{"title":"Discovery and evaluation of novel pyrrole/thiophene chalcone urea EGFR inhibitors via biological and docking studies.","authors":"Belma Zengin Kurt, Dilek Öztürk Civelek, Hümeyra Şahin Bektay, Ayşegül Özbilge Ulueren, Yakup Kolcuoğlu, Atilla Akdemir, Ahmet Fatih Şahin, Zeynep Durukan, Fatih Sönmez","doi":"10.1080/17568919.2025.2521249","DOIUrl":"10.1080/17568919.2025.2521249","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to synthesize novel chalcone-urea derivatives and evaluate their anticancer potential through antiproliferative, apoptotic, and epidermal growth factor receptor (EGFR) inhibitory activities, supported by molecular modeling.</p><p><strong>Materials & methods: </strong>Thirty-three chalcone-urea derivatives were synthesized in two series: pyrrole-chalcone ureas (<b>4a</b>-<b>4r</b>) and thiophene-chalcone ureas (<b>5a</b>-<b>5p</b>). Compounds were characterized using<sup>1</sup> H NMR, <sup>13</sup> C NMR, and mass spectrometry. Their antiproliferative effects were assessed against renal adenocarcinoma (769P), lung carcinoma (A549), colorectal adenocarcinoma (HT-29), and healthy kidney (HEK-293) cell lines. Selected compounds were further evaluated for EGFR inhibition, apoptotic activity, and cell cycle arrest. Molecular docking was performed to predict binding interactions with wild-type human EGFR.</p><p><strong>Results: </strong>Compounds <b>4e</b>, <b>4f</b>, and <b>4g</b> (pyrrole series) showed strong cytotoxicity against A549 and HT-29, while <b>5b</b>, <b>5c</b>, and <b>5d</b> (thiophene series) were effective on 769P. Compound <b>5c</b> exhibited the highest EGFR inhibition (IC₅₀ = 1 nM), potent apoptotic induction, and cell cycle arrest at the S phase in A549 cells. Docking studies confirmed favorable binding of <b>4r</b>, <b>5c</b>, and <b>5d</b> within the EGFR active site.</p><p><strong>Conclusions: </strong>Several chalcone-urea derivatives demonstrated potent anticancer properties, with compound 5c emerging as a promising EGFR inhibitor with strong cytotoxic and pro-apoptotic effects.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1423-1438"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527237","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}
引用次数: 0
Synthesis and docking of new Schiff-bases bearing urea as promising dual α-amylase and α-glucosidase inhibitors. 含尿素的新型希夫碱的合成与对接作为α-淀粉酶和α-葡萄糖苷酶双抑制剂。
IF 3.4 4区 医学
Future medicinal chemistry Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1080/17568919.2025.2520155
Sarah S Alammari, Fahd M Alminderej, Sabri Messaoudi, Haja Tar, Hamdoon A Mohammed, Suliman A Almahmoud, Ruba Al-Nemi, Mariusz Jaremko, Abdul-Hamid Emwas, Lotfi M Aroua
{"title":"Synthesis and docking of new Schiff-bases bearing urea as promising dual α-amylase and α-glucosidase inhibitors.","authors":"Sarah S Alammari, Fahd M Alminderej, Sabri Messaoudi, Haja Tar, Hamdoon A Mohammed, Suliman A Almahmoud, Ruba Al-Nemi, Mariusz Jaremko, Abdul-Hamid Emwas, Lotfi M Aroua","doi":"10.1080/17568919.2025.2520155","DOIUrl":"10.1080/17568919.2025.2520155","url":null,"abstract":"<p><strong>Aims: </strong>To synthesise and evaluate new amino biaryl-urea (<b>3a-h)</b> and Schiff base urea derivatives (<b>5a-h</b>) for their in vitro antidiabetic activity against α-glucosidase and α-amylase.</p><p><strong>Materials and methods: </strong>A series of Schiff base urea derivatives were synthesised through a two-step procedure: condensation of 4-chloro-o-phenylenediamine with isocyanates to form amino biaryl-urea derivatives (<b>3a-h</b>), followed by reaction with 2-hydroxy-naphthaldehyde. The new compounds were characterized using <sup>1</sup>H and <sup>13</sup>C NMR, as well as high-resolution mass spectrometry. Inhibition assays were conducted to determine IC<sub>50</sub> values of all compounds against α-amylase and α-glucosidase.</p><p><strong>Results: </strong>Derivatives <b>3g</b> and <b>3h</b> exhibited the strongest enzyme inhibition, with IC<sub>50</sub> values of 10.06 ± 0.32 µM (α-amylase) and 21.23 ± 1.27 µM (α-glucosidase), respectively. These compounds displayed activity comparable to the standard drug acarbose. Docking studies revealed that <b>3g</b> interacts with key residues TRP59 and GLN63 of α-amylase, supporting the experimental findings.</p><p><strong>Conclusions: </strong>The di-fluoro and di-chloro substituents in compounds <b>3g</b> and <b>3 h</b> enhance their antidiabetic activity, suggesting their potential as effective inhibitors of carbohydrate-metabolizing enzymes. Further studies are warranted to explore the therapeutic applications of these derivatives.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1241-1257"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505374","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}
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