European Journal of Medicinal Chemistry最新文献

{"title":"Hit to lead optimization of isopentenyl chalcones as novel MTHFD2 inhibitors for cancer treatment: design, synthesis, in-vitro, in-vivo and in-silico studies","authors":"Yingjie Hu ,&nbsp;Xiangli He ,&nbsp;Shuhui Li ,&nbsp;Tingting Zhang ,&nbsp;Jingjing Liao ,&nbsp;Ning Xu ,&nbsp;Yaxia Yuan ,&nbsp;Qi Wang ,&nbsp;Zhuo Chen ,&nbsp;Jin Huang ,&nbsp;Lei Ma","doi":"10.1016/j.ejmech.2025.117703","DOIUrl":"10.1016/j.ejmech.2025.117703","url":null,"abstract":"<div><div>Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays a key role in one-carbon metabolism, as it is highly upregulated in cancer cells while exhibiting minimal expression in healthy adult tissues. Consequently, MTHFD2 is regarded as a promising target for cancer therapies. In this study, a series of isopentenyl chalcones, based on hit compound sophoradin, were designed and synthesized by computer-aided drug design. Preliminary structure-activities relationship revealed the great significance of chalcone scaffold and isopentenyl groups. The optimized compound <strong>41</strong>, with an isopentenyl group and three hydroxyl groups, demonstrated remarkable activity and high selectivity in enzymatic assays (MTHFD1 IC₅₀ = 19.05 ± 7.10 μM, MTHFD2 IC₅₀ = 1.46 ± 0.28 μM, SI = 13). The cellular thermal shift assay implied that <strong>41</strong> could directly bind to MTHFD2. <em>In vitro</em>, compound <strong>41</strong> dramatically promoted intracellular ROS accumulation, and exhibited potent antiproliferative activity against lung cancer cells H1299 with low toxicity to BEAS-2B cells. Furthermore, <strong>41</strong> also demonstrated considerable anti-lung cancer efficacy in a mouse xenograft model and favorable pharmacokinetic properties without significant abnormalities in major organs. This work enriches the structure-activity relationship of MTHFD2 inhibitors and provides a potential candidate for cancer treatment.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117703"},"PeriodicalIF":6.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel benzamide derivatives with indole moiety as dual-target antiviral agents: Rational design, efficient synthesis, and potent anti-influenza activity through concurrent binding to PAC terminal domain and viral nucleoprotein","authors":"Chao Zhang ,&nbsp;Jia-Bin Li ,&nbsp;Yi-Wen Zhang ,&nbsp;Yun-Sang Tang ,&nbsp;Xiao-Fei Yu ,&nbsp;Qing-Guang Zhang ,&nbsp;Zhe Jin ,&nbsp;Shi-Cheng Hou ,&nbsp;Pang-Chui Shaw ,&nbsp;Chun Hu","doi":"10.1016/j.ejmech.2025.117681","DOIUrl":"10.1016/j.ejmech.2025.117681","url":null,"abstract":"<div><div>In this study, a series of benzamide derivatives with an indole moiety as dual-target inhibitors were designed, synthesized and evaluated against the RNA-dependent RNA polymerase (RdRp) complex of influenza viruses. The target compounds can simultaneously disrupt two key molecular interactions: the PA_C terminal domain and the nucleoprotein (NP) oligomerization. Through efficient synthesis and structure-activity relationship (SAR) analysis, compounds <strong>8e</strong> and <strong>8f</strong> as highly potent inhibitors were identified. Both compounds (<strong>8e</strong> and <strong>8f</strong>) exhibited submicromolar EC₅₀ values (1.64 ± 0.05 μM and 1.41 ± 0.27 μM) against influenza A virus (H1N1, A/WSN/33) and broad-spectrum activity against other influenza strains, including influenza B virus and multiple subtypes of influenza A. Notably, their cytotoxicity was significantly reduced compared to previous benzofurazan derivatives, with CC₅₀ values exceeding 100 μM. Surface plasmon resonance (SPR) experiments confirmed that <strong>8e</strong> and <strong>8f</strong> bound strongly to the PA C-terminal domain (KD = 8.90 μM and 4.82 μM) and NP (KD = 52.5 μM and 3.13 μM). Computational modeling approaches, including molecular docking, molecular dynamics (MD) simulations, and dynamical cross-correlation matrix (DCCM) analysis, principal component analysis (PCA) analysis and density functional theory (DFT) calculations, were employed to elucidate the putative binding modes and delineate critical interaction sites between the ligands and target proteins. These insights not only modulated subsequent structure-based lead optimization but also strengthened our understanding of the molecular determinants governing antiviral activity. This research provides a promising scaffold for developing dual-target antiviral agents with enhanced potency and safety, offering new strategies to combat influenza viruses.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"293 ","pages":"Article 117681"},"PeriodicalIF":6.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a novel sea snake antimicrobial peptide Hydrostatin-AMP3 with dual-mechanism against multidrug-resistant Klebsiella pneumoniae","authors":"Han-Yu Pan ,&nbsp;Rui-Wei Ye ,&nbsp;Sheng Han ,&nbsp;An Li ,&nbsp;Yong-Hong Zhou ,&nbsp;Ying-Ying Li ,&nbsp;Dan-Dan Yang ,&nbsp;Jia-Yi Lin ,&nbsp;Hao-Rui Dai ,&nbsp;Xia-Wen Dang ,&nbsp;Yue Cheng ,&nbsp;Zhi-Ping Zhao ,&nbsp;Zhao-Ran Yu ,&nbsp;Jun-Jie Wang ,&nbsp;Yu-Gang Zhuang ,&nbsp;Ying-Chuan Li ,&nbsp;Yi-Ming Lu","doi":"10.1016/j.ejmech.2025.117696","DOIUrl":"10.1016/j.ejmech.2025.117696","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) has ranked in the top three pathogens responsible for bacteria-related mortal infections. The emergence of multi-drug resistant (MDR) <em>K. pneumoniae</em> strains highlights an urgent need for novel antimicrobial agents. In this study, a series of antimicrobial peptides (AMPs) were screened based on gene annotation and sequence profiling via high-quality whole genome maps of sea snakes <em>Hydrophis curtus</em> and <em>Hydrophis cyanocinctus</em>. The most potent Hydrostatin-AMP3 showed efficient antimicrobial capacity against a panel of pathogenic bacteria, particularly MDR <em>K. pneumoniae</em> strains. Moreover, Hydrostatin-AMP3 exhibited remarkable efficacy in infection models of MDR <em>K. pneumoniae</em>, while demonstrating favourable profiles in safety and resistance development both in vitro and in vivo studies. Mechanistically, Hydrostatin-AMP3 exerted a bactericidal effect through a unique dual-mechanism: bacterial membrane disruption and DNA-targeting. Overall, this study presented Hydrostatin-AMP3 as the potential antimicrobial candidate for the treatment of MDR <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"293 ","pages":"Article 117696"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of benzothiazole aryl urea derivatives as potent anti-staphylococcal agents targeting autolysin-mediated peptidoglycan hydrolases","authors":"Long Zhou ,&nbsp;Miaoqing Xiang ,&nbsp;Yu Xin ,&nbsp;Shan Gao ,&nbsp;Kehan Xu ,&nbsp;Jing Zhang ,&nbsp;Xueer Lu ,&nbsp;Wenjian Tang","doi":"10.1016/j.ejmech.2025.117715","DOIUrl":"10.1016/j.ejmech.2025.117715","url":null,"abstract":"<div><div>Novel benzothiazole aryl ureas were designed and synthesized as <em>anti</em>-MRSA agents targeting peptidoglycan (PG) hydrolases (autolysins). Structural simplification of prior benzothiazole-urea hybrids yielded compounds <strong>4a</strong>, <strong>7a</strong> and <strong>11a</strong> bearing <em>p</em>-CF₃ on phenyl ring demonstrating narrow-spectrum activity against Gram-positive bacteria including clinical methicillin-resistant <em>S. aureus</em> (MRSA). The primary autolysin in <em>S. aureus</em>, AtlA, mediates peptidoglycan hydrolase activity critical for bacterial growth, division, and cell wall remodeling. Mechanistic studies revealed that <strong>4a</strong> down-regulated autolysin-related genes <em>RNAIII</em> and <em>walR</em>, disrupting peptidoglycan homeostasis. Knockout of <em>atlA</em> (a key autolysin gene) impaired <strong>4a</strong>′s efficacy, confirming autolysins as critical targets. Docking indicated that <strong>4a</strong> binds to AtlA <em>via</em> hydrogen bonds, Pi-Pi, and hydrophobic interactions. <em>In vivo</em>, <strong>4a</strong> significantly reduced bacterial load in a murine abdominal infection model, outperforming vancomycin at 10 mg/kg with lower cytotoxicity. Additionally, <strong>4a</strong> disrupted MRSA biofilms, suppressed hemolytic toxin production, and alleviated inflammation in infected mice. These findings underscore AtlA as a promising therapeutic target and highlight benzothiazole phenyl urea as a scaffold for developing innovative anti-staphylococcal agents.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117715"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Discovery of 3,4-dihydropyrimidine derivatives as novel Anti-PEDV agents targeting viral internalization through a unique calcium homeostasis disruption mechanism” [Europ. J. Med. Chem. 291 (2025) 117637]","authors":"Sai Lv ,&nbsp;Rumeng Ma ,&nbsp;Qun Tang ,&nbsp;Xiaoyang Wang ,&nbsp;Chunmei Wang ,&nbsp;Keyu Zhang ,&nbsp;Houkai Li ,&nbsp;Wenchong Ye ,&nbsp;Wen Zhou","doi":"10.1016/j.ejmech.2025.117683","DOIUrl":"10.1016/j.ejmech.2025.117683","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117683"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-regulated protein 94 (Grp94/gp96) in viral pathogenesis: Insights into its role and therapeutic potentials","authors":"Hao Xu,&nbsp;Brian S.J. Blagg","doi":"10.1016/j.ejmech.2025.117713","DOIUrl":"10.1016/j.ejmech.2025.117713","url":null,"abstract":"<div><div>Glucose-regulated protein 94 (Grp94/gp96) is endoplasmic reticulum (ER) resident form of the 90 kDa heat shock protein 90 (Hsp90) that is responsible for folding, maturation and stabilization of more than 400 client proteins. Grp94 has been implicated for various diseases including metastatic cancer, primary open-angle glaucoma, and infectious diseases. In fact, Grp94 plays critical roles in different stages of viral infection cycle. It chaperones receptor proteins and viral glycoproteins that are necessary for viral entry and replication. Beyond its role in protein homeostasis, Grp94 modulates host cellular processes such as apoptosis and immune responses, which are often exploited by viruses to sustain infection. This work provides an overview of the roles of Grp94 in viral pathogenesis across various viruses and its involvement in immune modulation with the development of Grp94-selective inhibitors and their potential as anti-viral therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117713"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel and highly potent anticancer agents enabled by selenium scanning of noscapine","authors":"Defeng Li ,&nbsp;Shuting Shen ,&nbsp;Chuanxu Liu ,&nbsp;Tingyu Guo ,&nbsp;Yuhuan Liu ,&nbsp;Peng Pan ,&nbsp;Xiaoyi Zhao ,&nbsp;Yiwen Ma ,&nbsp;Lei Li ,&nbsp;Shitao Huang ,&nbsp;Wenhao Shen ,&nbsp;YoupingZhang ,&nbsp;Biao Jiang ,&nbsp;Wei Wang ,&nbsp;Qianqian Yin ,&nbsp;Yongqiang Zhang","doi":"10.1016/j.ejmech.2025.117714","DOIUrl":"10.1016/j.ejmech.2025.117714","url":null,"abstract":"<div><div>Herein, the structural modification of noscapine via an elegant selenium scanning strategy has been demonstrated, which enables the production of three classes of novel seleno-containing noscapinoids, namely 6′, 7′, and 9′-seleno-substituted noscapines. Among them, 9′-seleno-substituted noscapines exhibited superior <em>in vitro</em> anti-proliferative activity, and 9′-cycloheptylselenomethyl-noscapine <strong>17a16</strong> with a large hydrophobic cycloheptyl group showed the most potent activity and good selectivity. Unlike most of the reported noscapinoids that induce G2/M phase arrest by targeting microtubules, <strong>17a16</strong> exhibited a distinct ability to induce S-phase arrest and displayed superior potency in inducing apoptosis, which attribute to the activation of two parallel checkpoint pathways orchestrating DNA damage response, including DNA-PKcs-dependent p53 stabilization and ATR-Chk1 axis activation. Dissecting the upstream mechanism revealed that <strong>17a16</strong> targets mitochondria and induces mitochondrial dysfunction. This study elucidates the interplay of mitochondrial stress, DNA damage response, p53 and ATR-Chk1 checkpoint activation in mediating the anticancer effects of <strong>17a16</strong>. Furthermore, <strong>17a16</strong> treatment significantly suppressed tumor growth in p53-deficient JeKo-1 subcutaneous xenograft model <em>in vivo</em>, without inducing systemic toxicity. Overall, our findings highlight <strong>17a16</strong> as a promising lead compound in cancer therapy and demonstrate the potential of selenium scanning as a valuable strategy for anticancer drug discovery.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"293 ","pages":"Article 117714"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, anticancer activity evaluation and molecular dynamics study of pyrazine N-oxide-based SHP2 allosteric inhibitors","authors":"Xin Wang ,&nbsp;Xiaoyu Shao ,&nbsp;Meijing Wang ,&nbsp;Yan Li ,&nbsp;Tongtong Geng ,&nbsp;Yashuai Wang ,&nbsp;Xuyang Ding ,&nbsp;Yichao He ,&nbsp;Hongwei Jin ,&nbsp;Yang Sun ,&nbsp;Zhongjun Li ,&nbsp;Xiangbao Meng","doi":"10.1016/j.ejmech.2025.117687","DOIUrl":"10.1016/j.ejmech.2025.117687","url":null,"abstract":"<div><div>Src homology-2-containing protein tyrosine phosphatase 2 (SHP2), the first oncoprotein identified in the protein phosphatase family, has emerged as a promising anticancer target in recent years. Here, we report the discovery of a novel series of pyrazine <em>N</em>-oxide derivatives as potent SHP2 allosteric inhibitors and the identification of compound <strong>C5</strong> as a highly potent and selective SHP2 allosteric inhibitor (SHP2^WT IC₅₀ = 0.023 μM, SHP2^E76K IC₅₀ = 0.119 μM). At the cellular level, <strong>C5</strong> exerted significant antiproliferative effect on KYSE-520 and MV-411 cells (KYSE-520 IC₅₀ = 6.97 μM, MV-411 IC₅₀ = 0.67 μM) and induced apoptosis of MV-411 cells by downregulating the SHP2-mediated ERK cell signaling. Molecular dynamics simulations revealed that <strong>C5</strong> could form stable hydrogen bond interactions, cation-π interactions and water bridges with key residues Glu110, Arg111, Phe113, Gly115 and Thr253, thereby effectively binding to the tunnel allosteric site of SHP2. Notably, the pyrazine <em>N</em>-oxide scaffold could additionally form a strong and stable hydrogen bond with Arg111. Collectively, this work uncovers a novel and potent scaffold as well as presents compound <strong>C5</strong> as a promising lead for the development of new chemotypes of SHP2 allosteric inhibitors.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"293 ","pages":"Article 117687"},"PeriodicalIF":6.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of isatin-functionalized benzenesulfonamides as novel carbonic anhydrase II and VII inhibitors with antiepileptic potential","authors":"Wagdy M. Eldehna ,&nbsp;Anwar A. El-Hamaky ,&nbsp;Simone Giovannuzzi ,&nbsp;Zainab M. Elsayed ,&nbsp;Mahmoud Abdelrahman Alkabbani ,&nbsp;Eman F. Khaleel ,&nbsp;Mohammad M. Al-Sanea ,&nbsp;Mahmoud F. Abo-Ashour ,&nbsp;Yosra S.R. Elnaggar ,&nbsp;Alessio Nocentini ,&nbsp;Claudiu T. Supuran ,&nbsp;Haytham O. Tawfik","doi":"10.1016/j.ejmech.2025.117706","DOIUrl":"10.1016/j.ejmech.2025.117706","url":null,"abstract":"<div><div>Epilepsy continues to be a challenging neurological disorder with a partially understood etiology that necessitates novel therapeutic strategies. This study introduces isatin-functionalized benzenesulfonamides (<strong>5a-f</strong> and <strong>7a-e</strong>) targeting carbonic anhydrase (CA) isoforms II and VII implicated in seizure mechanisms. The design exploits a one-tail approach, integrating a sulfonamide warhead for zinc coordination in the CA active site, a triazole linker (inspired by FDA-approved antiepileptic rufinamide), and an isatin-based tail. <em>In vitro</em> evaluation revealed potent inhibition of hCA II and VII, with sulfonamides <strong>5c</strong>, <strong>5e</strong>, <strong>5f</strong>, <strong>7a</strong>, and <strong>7d</strong> showing notable activity. The anticonvulsant activity of five carbonic anhydrase inhibitors (<strong>5c</strong>, <strong>5e</strong>, <strong>5f</strong>, <strong>7a</strong>, and <strong>7d</strong>) was assessed using PTZ and pilocarpine-induced convulsions in mice. These compounds were selected based on their superior <em>in vitro</em> inhibitory potency against hCA II and VII isoforms, as reflected by their low nanomolar K_I values. Among them, <strong>5e</strong> and <strong>7a</strong> exhibited the highest efficacy, achieving 100 % protection in the PTZ model and significantly delaying seizure onset in the pilocarpine model. These compounds also reduced seizure severity and improved survival rates, surpassing valproic acid's effectiveness. Additionally, biochemical evaluation revealed that both compounds restored hippocampal KCC2 and mTOR levels, suggesting their role in modulating neuronal excitability and ionic balance. Safety assessments, including Rotarod and biochemical toxicity tests, confirmed their favorable safety profile, supporting their potential as promising anticonvulsant candidates.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117706"},"PeriodicalIF":6.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the discovery of copper(II) complexes as potential anticancer drugs","authors":"Bartłomiej Rogalewicz,&nbsp;Agnieszka Czylkowska","doi":"10.1016/j.ejmech.2025.117702","DOIUrl":"10.1016/j.ejmech.2025.117702","url":null,"abstract":"<div><div>This review article offers a literature search of the most active, new copper (II) anticancer complexes based on nitrogen-containing ligands, reported in the literature over the past 5 years: from the beginning of 2019, until mid-2024. In the modern world, cancer remains one of the deadliest diseases of all. Although years of the ongoing research allowed us to better understand its nature, and thus aim more precisely at specific molecular targets and pathways, many of its aspects remain unclear. Today, chemotherapy still remains at the forefront of cancer treatment. With the ever-growing struggles to overcome chemoresistance and occurrence of serious side effects, the discovery of new, more selective and active drugs is a task of an utmost importance. At the same time, copper (II)-based compounds offer a wide array of biological activities and valuable biochemical properties. This review article provides the update on the recent advances in the discovery of new potential anticancer drugs among copper (II)-based compounds in the recent five years.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"292 ","pages":"Article 117702"},"PeriodicalIF":6.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}