Future medicinal chemistry最新文献

Synthesis of benzenesulfonamide derivatives reveals anti-CCSCs activity by regulating Wnt/β-catenin pathway. 苯磺酰胺衍生物的合成通过调节Wnt/β-catenin通路揭示了抗ccscs的活性。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-03 DOI: 10.1080/17568919.2026.2726190

Xueyu Wang, Kaili Wang, Quanxing Zhong, Hao Yang, Yinan Zhang, Dong Wang, Yan Wu, Haijuan Qin, Baiwang Chu, Yiwen Duan, Peng Yu, Can Liu, Hua Sun

{"title":"Synthesis of benzenesulfonamide derivatives reveals anti-CCSCs activity by regulating Wnt/β-catenin pathway.","authors":"Xueyu Wang, Kaili Wang, Quanxing Zhong, Hao Yang, Yinan Zhang, Dong Wang, Yan Wu, Haijuan Qin, Baiwang Chu, Yiwen Duan, Peng Yu, Can Liu, Hua Sun","doi":"10.1080/17568919.2026.2726190","DOIUrl":"https://doi.org/10.1080/17568919.2026.2726190","url":null,"abstract":"Background: Colorectal cancer (CRC) has become one of the most common causes of cancer mortality worldwide. Accumulating studies suggest that the progressive up-regulation of Wnt/β-catenin signaling is a crucial hallmark of CRC, and this pathway is involved in the development and maintenance of colorectal cancer stem cells (CCSCs). Therefore, inhibition of its activity may be an effective strategy for the treatment of CRC.Methods: Based on the reported structural characteristics of LF3 which is a small molecule inhibitor of β-catenin/Transcription Factor 4 (TCF4) and the significant role of the naphthoquinone group in anti-tumor activity, we designed and synthesized a series of benzenesulfonamide derivatives.Results: The results of anti-CRC activity showed that compound 3gg has anti-proliferation and anti-CCSCs activities by regulating the Wnt/β-catenin signaling pathway in vitro. In addition, compound 3gg could inhibit CCSCs activity through regulating the Wnt/β-catenin signaling pathway in xenografts.Conclusion: Compound 3gg, which inhibits CCSCs and Wnt/β-catenin signaling pathway activity, could be a promising lead compound for further investigation as a potential anti-cancer agent.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-21"},"PeriodicalIF":3.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886283","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}

引用次数: 0

Rational drug design, synthetic and artificial intelligence approaches for bioactive heterocycles: advances and perspectives. 生物活性杂环化合物的合理药物设计、合成和人工智能方法：进展与展望。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-02 DOI: 10.1080/17568919.2026.2726188

Debajit Dewan, Bhupender Nehra, Rajarshi Nath, Sumel Ashique, Md Jawaid Akhtar, Ekta Khare, Sheetu Wadhwa, Sabina Yasmin, Biplab Debnath, Md Yousuf Ansari

{"title":"Rational drug design, synthetic and artificial intelligence approaches for bioactive heterocycles: advances and perspectives.","authors":"Debajit Dewan, Bhupender Nehra, Rajarshi Nath, Sumel Ashique, Md Jawaid Akhtar, Ekta Khare, Sheetu Wadhwa, Sabina Yasmin, Biplab Debnath, Md Yousuf Ansari","doi":"10.1080/17568919.2026.2726188","DOIUrl":"https://doi.org/10.1080/17568919.2026.2726188","url":null,"abstract":"Heterocyclic scaffolds are vital to medicinal chemistry due to their versatility, diversity, and ability to target various biological molecules. This review covers advances in designing and synthesizing bioactive heterocycles, highlighting structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches with computational modeling and Artificial Intelligence (AI) to find potent, selective molecules with good Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profiles. Case studies show the successful development of heterocyclic drugs for cancer, microbial infections, inflammation, viral infections, and Central Nervous System (CNS) disorders. Synthetic methods have evolved from classical electrophilic/nucleophilic reactions to modern techniques like multicomponent reactions, microwave synthesis, metal catalysis, and green chemistry, making frameworks more accessible. The review discusses Quantitative Structure-Activity Relationship (QSAR) studies for molecular optimization. Challenges like synthetic complexity and resistance remain, but emerging trends like machine learning, omics, and enzyme synthesis offer new opportunities. Ultimately, combining design principles and innovative methods can speed up drug discovery and enable sustainable, personalized therapies with heterocyclic pharmacophores.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-23"},"PeriodicalIF":3.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873252","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}

引用次数: 0

Advancing cancer drug discovery through the integration of machine learning and high-throughput screening. 通过整合机器学习和高通量筛选，推进癌症药物的发现。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-14 DOI: 10.1080/17568919.2026.2714025

Kamil Herbetko, Katarzyna Herbetko, Magdalena Mikołajek, Laura Wojdyło, Karolina Klasen, Marek Kulbacki, Julita Kulbacka

{"title":"Advancing cancer drug discovery through the integration of machine learning and high-throughput screening.","authors":"Kamil Herbetko, Katarzyna Herbetko, Magdalena Mikołajek, Laura Wojdyło, Karolina Klasen, Marek Kulbacki, Julita Kulbacka","doi":"10.1080/17568919.2026.2714025","DOIUrl":"10.1080/17568919.2026.2714025","url":null,"abstract":"Cancer drug discovery is a complex process that requires identifying compounds that selectively target malignant cells. While high-throughput screening (HTS) is essential for testing large libraries, it generates vast datasets that are difficult to interpret. Recently, the integration of artificial intelligence (AI), particularly deep learning (DL), has significantly accelerated drug candidate selection. This review highlights the synergy between AI and HTS, emphasizing DL techniques such as convolutional neural networks for bioactivity prediction, recurrent neural networks for de novo design, and reinforcement learning for property optimization. These methods streamline preclinical research by enabling rapid multi-omics analysis and prediction of drug-target interactions. However, challenges regarding data quality, model interpretability, and ethics persist. Emerging paradigms like Explainable AI and federated learning aim to enhance transparency and collaboration while safeguarding privacy. Ultimately, overcoming these barriers through AI-HTS integration holds transformative potential to reduce development costs and improve clinical outcomes for cancer patients.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2403-2424"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758260","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}

引用次数: 0

From design to functionality of ionic-liquid-related salts: DNA titration, antioxidants, and anticancer activities. 从离子液体相关盐的设计到功能：DNA滴定、抗氧化剂和抗癌活性。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-05 DOI: 10.1080/17568919.2026.2714030

Salim Ali, Ming-Fa Hsieh, Zheng-Yuan Su, Mouslim Messali, Noureddine El Messaoudi, Shilpi Khurana, Imran Ali

{"title":"From design to functionality of ionic-liquid-related salts: DNA titration, antioxidants, and anticancer activities.","authors":"Salim Ali, Ming-Fa Hsieh, Zheng-Yuan Su, Mouslim Messali, Noureddine El Messaoudi, Shilpi Khurana, Imran Ali","doi":"10.1080/17568919.2026.2714030","DOIUrl":"10.1080/17568919.2026.2714030","url":null,"abstract":"Aims: To develop effective functional ionic-liquid-related salts (ILRSs) as future anticancer drugs.Materials and methods: Twelve imidazole-based ionic-liquid-related salts were synthesized and characterized by spectroscopic methods. These ILRSs were used to study the antioxidant and anticancer activities, DNA titration, modeling, and in-silico studies.Results: Among 12 ILRSs, ILRSs 5 and 4 indicated superior activities, showing higher scavenging percentages (70.7% and 65.5%) and lower IC50 values than the standard ascorbic acid. ILRSs 5 and 4 showed the most effective activities with MCF-7 cells, with viability values of 52.17% and 53.67% at 10 µM and IC50 values of 10.87 and 11.03 µM, respectively. DNA-binding studies showed moderate to strong interactions with Ct-DNA (binding constants: 104 to 105 M-1). The modeling studies of compounds A and B with DNA confirmed one hydrogen bond with -8.7 and -8.2 kcal/mol binding affinities.Conclusions: The reported ILRSs 5 and 4 showed good antioxidant and anticancer activities and may be used as future anticancer drugs.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2373-2387"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673355","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}

引用次数: 0

Designing organometallic complexes to induce immunogenic cell death. 设计有机金属配合物诱导免疫原性细胞死亡。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-05 DOI: 10.1080/17568919.2026.2714019

Thomas Scattolin

引用次数: 0

Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureus. 不对称苯并唑衍生物作为抗金黄色葡萄球菌的双抗生物膜和抗壁磷壁酸剂。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-10 DOI: 10.1080/17568919.2026.2714028

Mine Buga Aktekin, Zehra Oksuz, Mehmet Abdullah Alagoz, Bahar Uluca Han, Oztekin Algul

{"title":"Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureus.","authors":"Mine Buga Aktekin, Zehra Oksuz, Mehmet Abdullah Alagoz, Bahar Uluca Han, Oztekin Algul","doi":"10.1080/17568919.2026.2714028","DOIUrl":"10.1080/17568919.2026.2714028","url":null,"abstract":"Aims: Antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), have renewed interest in antivirulence strategies. This study aimed to design, synthesize, and evaluate asymmetric di‑heterocyclic benzazole derivatives as antibiofilm agents targeting wall teichoic acid (WTA) biosynthesis.Materials and methods: Twenty‑one novel bis‑heterocyclic benzazole derivatives bearing an ethyl‑thio linker were synthesized and characterized. Antibacterial activity was determined by broth microdilution. Antibiofilm activity (inhibition and eradication) was assessed at sub‑minimal inhibitory concentrations (sub‑MICs) using crystal violet. Molecular docking and 200 ns molecular dynamics (MD) simulations were performed against key WTA enzymes (TarGH, TarS, TarM, TarL, and TarJ).Results: Compounds 18, 21, 23, and 24 showed potent antibacterial activity against methicillin‑susceptible S. aureus (MSSA) and MRSA, with MIC values as low as 15.62 µg/mL. All selected compounds significantly inhibited biofilm at sub‑MIC levels. Compound 24 was most effective, with an MBIC50 of 3.90 µg/mL against MSSA and eradicated pre‑formed biofilms at 7.81 µg/mL. Docking and MD simulations revealed stable interactions of compounds 23 and 24 with TarGH and TarS, suggesting a WTA‑targeting mechanism.Conclusions: Di‑heterocyclic benzazole derivatives, especially compound 24, are promising scaffolds for antibiofilm agents against S. aureus. Our findings support further mechanistic and preclinical evaluation as potential antivirulence therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2337-2355"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701115","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}

引用次数: 0

Design and development of 2,7-disubstituted 6-methoxyquinazolin-4 (3H)-ones as potential anti-cancer agents possibly through downregulation of Wnt/β-catenin/TCF4 signaling pathway. 2,7-二取代6-甲氧基喹唑啉-4 (3H)- 1可能通过下调Wnt/β-catenin/TCF4信号通路而成为潜在的抗癌药物。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1080/17568919.2026.2714576

Prashant R Murumkar, Kaushik Neogi, Premlal Meher, Rasana Yadav, Karan Joshi, Omkumar Prajapati, Priyanshu Sharma, Poonam Yadav, Devarajan Karunagaran, Prasanta Kumar Nayak, Mange Ram Yadav

{"title":"Design and development of 2,7-disubstituted 6-methoxyquinazolin-4 (3H)-ones as potential anti-cancer agents possibly through downregulation of Wnt/β-catenin/TCF4 signaling pathway.","authors":"Prashant R Murumkar, Kaushik Neogi, Premlal Meher, Rasana Yadav, Karan Joshi, Omkumar Prajapati, Priyanshu Sharma, Poonam Yadav, Devarajan Karunagaran, Prasanta Kumar Nayak, Mange Ram Yadav","doi":"10.1080/17568919.2026.2714576","DOIUrl":"10.1080/17568919.2026.2714576","url":null,"abstract":"Aim: A novel series of 2,7-disubstituted 6-methoxyquinazolin-4(3H)-one derivatives were designed, synthesized, and evaluated for in-vitro anti-cancer potential.Methods: Compounds were docked, synthesiazed and then evaluated for in vitro anti-cancer activity using the sulforhodamine B assay in HCT116 and HepG2 cells. Apoptosis induction was analyzed via morphological changes, Hoechst 33342, and Annexin V/PI staining. The effect on β-catenin/TCF‑mediated transcriptional activity was assessed by TOPFlash/FOPFlash assay, TCF4 and β-catenin protein expression by immunocytofluorescence, and Wnt target genes (like c-MYC and Cyclin D1) mRNA levels by RT-PCR against HCT116 cells. Furthermore, In vitro anti-cancer potential was evaluated against primary human gallbladder cancer cells.Results: The derivatives showed favorable binding with the active site residues on β-catenin and have the potential to disrupt the β-catenin/TCF4 interaction. Most of them have comparable anti-cancer activity to imatinib mesylate. Compound 42D, one of the potent compounds (IC50: 3.89 μM in HCT116; 8.28 μM in HepG2), induced apoptosis, and significantly downregulated β-catenin/TCF4 signaling and downstream targets (c-Myc, Cyclin D1) in HCT116 cells and this could be one of the mechanisms by which it exerts its anti-cancer activity. It showed anti-cancer activity in primary gallbladder cancer cells (IC50: 7.26 μM).Conclusion: Compound (42D) represents a promising molecule as an anti-cancer agent against colon, hepatocellular, and gallbladder cancers targeting the Wnt/β-catenin/TCF4 signaling pathway.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2285-2299"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758487","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}

引用次数: 0

In silico and in vitro evaluation of new sulfonamide derivatives as VEGFR-2 inhibitors for cancer therapy. 新的磺胺衍生物作为VEGFR-2抑制剂用于癌症治疗的硅和体外评价。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-25 DOI: 10.1080/17568919.2026.2718764

Ahmed Wheed Radhi, Hayder Ghanim Chfat, Zahraa Sabbar Omarn, Hayder Kadhim Abbas, Ali Jabbar Radhi, Ehab K Obaid

{"title":"In silico and in vitro evaluation of new sulfonamide derivatives as VEGFR-2 inhibitors for cancer therapy.","authors":"Ahmed Wheed Radhi, Hayder Ghanim Chfat, Zahraa Sabbar Omarn, Hayder Kadhim Abbas, Ali Jabbar Radhi, Ehab K Obaid","doi":"10.1080/17568919.2026.2718764","DOIUrl":"10.1080/17568919.2026.2718764","url":null,"abstract":"Vascular endothelial growth factor receptor 2 (VEGFR-2) is a principal regulator of tumor progression and angiogenesis, which makes it an attractive target for developing and creating anticancer agents. A series of sulfonamide-derived compounds (K1-K5) were designed and evaluated for their ability to inhibit VEGFR-2 and for their cytotoxic activity against HCT-116 (colon), HepG-2 (liver), MCF-7 (breast) human cancer cells, and WI-38 (normal) fibroblasts. All of the compounds produced significant inhibition of VEGFR-2, with IC50values ranging from 0.0917 ± 0.028 µM (K5) to 1.2007 ± 0.013 µM (K1), relative to Sorafenib (IC50 = 0.0525 ± 0.017 µM). The most promising compound was K4, which produced potent inhibition of VEGFR-2 (IC50 = 0.1717 ± 0.027) and the highest selectivity index (SI) of all tested compounds: 25.6 (HCT-116), 14.8 (HepG-2), and 17.0 (MCF-7). In contrast to Sorafenib, whose Selectivity Index (SI) values range between 2.1 and 4.9, the SI values of both Vinblastine and Doxorubicin are less than 2.0 across these particular cell lines. This suggests that K4 has 12 times greater selectivity than Sorafenib and over 25 times greater selectivity than traditional chemotherapeutics. The increased selectivity of K4 can be attributed to the incorporation of a urea-linked sulfonamide moiety, which allows for the formation of hydrogen bonds and minimizes nonspecific hydrophobic interactions. Collectively, these data will demonstrate the importance of designing sulfonamide analogues with optimal structural characteristics to identify effective and specific VEGFR-2 inhibitors and that K4 represents a potentially important candidate for continued preclinical development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2357-2371"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812282","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}

引用次数: 0

Novel thioether and thioester-based derivatives as promising antibacterial agents with antioxidant potential: design, synthesis, and in silico studies. 新型硫醚和硫酯基衍生物作为具有抗氧化潜力的有前途的抗菌剂：设计，合成和硅研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1080/17568919.2026.2714020

Aya H Othman, Menna M A Abd El-Mageed, Faten Farouk, Ayman B Farag, Safinaz E-S Abbas

{"title":"Novel thioether and thioester-based derivatives as promising antibacterial agents with antioxidant potential: design, synthesis, and in silico studies.","authors":"Aya H Othman, Menna M A Abd El-Mageed, Faten Farouk, Ayman B Farag, Safinaz E-S Abbas","doi":"10.1080/17568919.2026.2714020","DOIUrl":"10.1080/17568919.2026.2714020","url":null,"abstract":"Aim: Development of novel thioethers (5a-g), thioesters (6a-g), and bis-thioethers (8a-h) with antibacterial potential.Materials and methods: Twenty-one novel compounds were synthesized and evaluated for antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Compounds with significant antibacterial activity were estimated for antioxidant potential and in silico studies.Results and discussion: Eight of the tested compounds demonstrated significant antibacterial activity, particularly versus B. cereus and S. aureus. The minimum inhibitory concentration (MIC) revealed the remarkable antibacterial activity and bactericidal behavior, as demonstrated by minimum bactericidal concentration (MBC) determination and time-kill kinetics studies of 8g and 8h, against S. aureus. Moreover, both compounds exhibited notable antibiofilm activity against S.aureus. Selectivity of the tested compounds as antibacterial agents was confirmed by low cytotoxicity toward normal cells. Remarkably, compounds 8b and 8g exhibited antioxidant potential (ABTS and DPPH) assays in comparison to ascorbic acid. Evaluation of antioxidant markers revealed that 8g displayed an increase in superoxide dismutase (SOD) and malondialdehyde (MDA) level. In silico studies revealed that the compounds exhibited acceptable ADME properties, with strong binding to the bacterial dihydrofolate reductase active site, along with dynamic stability of the DHFR-8g complex.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2301-2318"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705994","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

EGFR kinase inhibitors from novel thiazole derivatives: synthesis, anticolon cancer, docking, and ADME studies. 来自新型噻唑衍生物的EGFR激酶抑制剂：合成、抗结肠癌、对接和ADME研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 DOI: 10.1080/17568919.2026.2726191

Amani M R Alsaedi, Alaa M Abu Alnjaa, Amel S Younes, Zeinab A Muhammad, Sami A Al-Hussain, Magdi E A Zaki, Thoraya A Farghaly

{"title":"EGFR kinase inhibitors from novel thiazole derivatives: synthesis, anticolon cancer, docking, and ADME studies.","authors":"Amani M R Alsaedi, Alaa M Abu Alnjaa, Amel S Younes, Zeinab A Muhammad, Sami A Al-Hussain, Magdi E A Zaki, Thoraya A Farghaly","doi":"10.1080/17568919.2026.2726191","DOIUrl":"https://doi.org/10.1080/17568919.2026.2726191","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is a key regulator of malignant cell growth and survival, making it an attractive target for cancer therapy. In this study, a new series of thiazole derivatives was rationally designed and synthesized as potential EGFR inhibitors and evaluated for their antiproliferative activity against two human colon cancer cell lines (HCT-116 and HT29). Several compounds exhibited potent anticancer activity, with compound 4j showing the highest potency, displaying half-maximal inhibitory concentration (IC50) values of 2.10 and 1.91 µM against HCT-116 and HT29 cells, respectively. Owing to its superior antiproliferative activity, compound 4j was further evaluated for EGFR inhibitory activity and demonstrated remarkable potency with an IC50 value of 0.27 µM. In addition, 4j exhibited a favorable selectivity index toward normal WI38 cells and effectively induced apoptosis through modulation of Bax, Bcl-2, and p53 expression. Molecular docking demonstrated strong binding interactions of 4j within the EGFR active site, while its ADME predictions supported its favorable drug-like profile. Overall, compound 4j represents a promising lead candidate for the development of novel EGFR-targeted anticancer agents.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864343","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}

引用次数: 0