European Journal of Medicinal Chemistry最新文献

{"title":"Furazanopyrazine-based novel promising anticancer agents interfering with the eicosanoid biosynthesis pathways by dual mPGES-1 and sEH inhibition","authors":"Gianluigi Lauro ,&nbsp;Michela Aliberti ,&nbsp;Mauro De Nisco ,&nbsp;Silvana Pedatella ,&nbsp;Giacomo Pepe ,&nbsp;Manuela Giovanna Basilicata ,&nbsp;Maria Giovanna Chini ,&nbsp;Katrin Fischer ,&nbsp;Robert K. Hofstetter ,&nbsp;Oliver Werz ,&nbsp;Maria Grazia Ferraro ,&nbsp;Marialuisa Piccolo ,&nbsp;Carlo Irace ,&nbsp;Anella Saviano ,&nbsp;Pietro Campiglia ,&nbsp;Alessia Bertamino ,&nbsp;Carmine Ostacolo ,&nbsp;Tania Ciaglia ,&nbsp;Michele Manfra ,&nbsp;Giuseppe Bifulco","doi":"10.1016/j.ejmech.2025.117402","DOIUrl":"10.1016/j.ejmech.2025.117402","url":null,"abstract":"<div><div>We report the identification of a new set of compounds based on the furazanopyrazine core interfering with eicosanoid biosynthesis and acting as potentially effective anti-inflammatory and anticancer agents. Based on our previous promising results on a set of furazanopyrazine-based compounds against the microsomal prostaglandin E₂ synthase-1 (mPGES-1) enzyme, we here identified derivatives with improved pharmacokinetic properties by replacing the ester moiety with a more stable ether group.</div><div>A focused virtual library of 1 × 10⁴ molecules was built and screened against mPGES-1 through molecular docking experiments, leading to the selection of 10 candidates for synthesis and biological evaluation. Several molecules were found to inhibit mPGES-1 and, among them, two items featured IC₅₀ values in the low micromolar range. Additional computational studies on the collection of synthesized compounds demonstrated that compound <strong>3b</strong>, previously emerged as an mPGES-1 inhibitor, interfered with soluble epoxide hydrolase (sEH) activity, thus emerging as a valuable dual mPGES-1/sEH inhibitor. The pharmacokinetic features of the most potent compounds were accurately estimated. Unfortunately, poor outcomes were obtained for <strong>3b</strong>; on the other hand, compound <strong>7e</strong> exhibited promising mPGES-1 inhibition and excellent pharmacokinetic profile, demonstrating that the novel furazanopyrazine-based items with ether moiety possess improved pharmacokinetic properties compared to the ester-based compounds reported in our previous study. Additionally, the anticancer properties of <strong>7e</strong> and <strong>7d</strong>, the latter emerged as the most active mPGES-1 inhibitor, were evaluated and both compounds showed promising activities against HCT-116 human colorectal cancer (CRC) cells.</div><div>These findings highlight the furazanopyrazine core as a promising scaffold for disclosing new anti-inflammatory drugs with the ability to inhibit targets belonging to arachidonic acid cascade.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"289 ","pages":"Article 117402"},"PeriodicalIF":6.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GreenMedChem-inspired light-air mediated C(sp3)-H bond oxidation: A new tool for isoquinolone synthesis","authors":"Qi Zhang,&nbsp;Wenbing Dai,&nbsp;Da-Le Guo,&nbsp;Hao Chen,&nbsp;Xilei Wang,&nbsp;Ruiran Xu,&nbsp;Juan Liu,&nbsp;Mei-Mei Li,&nbsp;Yun Deng","doi":"10.1016/j.ejmech.2025.117414","DOIUrl":"10.1016/j.ejmech.2025.117414","url":null,"abstract":"<div><div>Isoquinolone represents a significant and promising molecular scaffold for drug development. As green chemistry advances, light-mediated C(<em>sp</em>³)-H bond oxidation has emerged as a pivotal tool for medicinal chemists in constructing isoquinolone framework and enabling late-stage functionalization. However, existing methods often rely on metal catalysts, hazardous peroxides, dye sensitizers, or high-temperature atmosphere, which pose environmental concerns. Inspired by “GreenMedChem”, we initially developed a light-air mediated C(<em>sp</em>³)-H bond oxidation strategy for isoquinolone framework constructing, which offers the benefits of straightforward operation, mild reaction conditions, atomic economy, and broad substrate scope. A total of 54 isoquinolones were obtained, achieving a yield of up to 97 % under ambient conditions, using air as the sole oxygen source, and the ²H NMR analysis further verified that water was the only byproduct. Subsequently, three pharmacological agents were prepared via the late-stage C–H bond oxidation strategy.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117414"},"PeriodicalIF":6.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443945","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 pyrimidinetrione derivatives as DprE1 inhibitors with potent antimycobacterial activities","authors":"Jing Liang ,&nbsp;Yang Liu ,&nbsp;Qing Guan ,&nbsp;Yan Li ,&nbsp;Meng-Zhu Zheng ,&nbsp;Xiao-Lian Zhang ,&nbsp;Li-Xia Chen ,&nbsp;Hua Li","doi":"10.1016/j.ejmech.2025.117416","DOIUrl":"10.1016/j.ejmech.2025.117416","url":null,"abstract":"<div><div>Tuberculosis (TB) is one of the ten major factors threatening human life and health. At present, many factors limit the application of existing anti-tuberculosis drugs, such as a small range of available drug options, poor treatment compliance, and severe toxic and side effects. It is extremely urgent to develop novel anti-tuberculosis drugs. DprE1 is a potential anti-mycobacterial cell wall target, and some DprE1 inhibitors have entered the clinical research stage. Our research group found DprE1 inhibitor <strong>G50</strong> with similar activity as isoniazid through virtual screening in the early stage. To obtain better DprE1 inhibitors, 45 new compounds were designed and synthesized based on the structure of <strong>G50</strong>. Among them, 12 selected DprE1 enzyme inhibitors could significantly inhibit the growth of <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) H37Ra and H37Rv growth <em>in vitro</em>. The MIC₅₀ value of compound <strong>42</strong> against <em>M.tb</em> H37Ra is 1.071 ± 0.041 μM, with the selective index (SI) value of 186.74 (the SI value of linezolid is 119.9). Compared to <strong>G50</strong>, compound <strong>42</strong> exhibits a 5-fold increase in DprE1 enzyme inhibitory activity. In addition, the binding affinity of compound <strong>42</strong> is equivalent to that of <strong>G50</strong>. This study further enriches the examples of developing DprE1 inhibitors based on the backbone of pyrimidinetrione and also provides potential anti-tuberculosis lead compounds.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"289 ","pages":"Article 117416"},"PeriodicalIF":6.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443944","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 potent indole-3-carboxamide autotaxin inhibitors with preferred lipophilicity for in vivo treatment of pulmonary fibrosis","authors":"Deyi Ma ,&nbsp;Nan Jiang ,&nbsp;Jiachen Zhang,&nbsp;Hongrui Lei,&nbsp;Xin Zhai","doi":"10.1016/j.ejmech.2025.117398","DOIUrl":"10.1016/j.ejmech.2025.117398","url":null,"abstract":"<div><div>Autotaxin (ATX), a major source of the lipid mediator lysophosphatidic acid (LPA), plays a critical role in the pathogenesis and progression of pulmonary fibrosis. In this study, with the aim of developing novel ATX inhibitors with preferred lipophilicity, structure-based optimizations of PAT-409 were carried out, leading to the identification of two novel orally active ATX inhibitors, <strong>4</strong> and <strong>29</strong>, with IC₅₀ values of 1.5 nM and 1.08 nM, respectively. Both compounds demonstrated favorable physicochemical properties and desirable ADMET profiles. Notably, compounds <strong>4</strong> and <strong>29</strong> exhibited excellent <em>in vitro</em> metabolic stability (<em>t</em>_<em>1/2</em> &gt; 170 min) and negligible cytotoxicity. Furthermore, oral administration of either compound <strong>4</strong> or <strong>29</strong> (60 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to PAT-409 (60 mg/kg) in a bleomycin-induced pulmonary fibrosis mouse model, suggesting their potential as promising anti-pulmonary fibrosis agents for further development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117398"},"PeriodicalIF":6.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435374","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":"Phytomolecules as Alzheimer's therapeutics: A comprehensive review","authors":"Mohd Kamil Hussain ,&nbsp;Moazzam Ahmad ,&nbsp;Shahnaaz Khatoon ,&nbsp;Mohsin Vahid Khan ,&nbsp;Sarfuddin Azmi ,&nbsp;Md Arshad ,&nbsp;Shakir Ahamad ,&nbsp;Mohammad Saquib","doi":"10.1016/j.ejmech.2025.117401","DOIUrl":"10.1016/j.ejmech.2025.117401","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a leading neurodegenerative disorder recognized by progressive cognitive decline and behavioral changes. The pathology of AD is characterized by the accumulation of amyloid-β (Aβ) plaques and the hyperphosphorylation of tau protein, which leads to synaptic loss and subsequent neurodegeneration. Additional contributors to disease progression include metabolic, vascular, and inflammatory factors. Glycogen synthase kinase-3β (GSK-3β) is also implicated, as it plays a crucial role in tau phosphorylation and the progression of neurodegeneration. This review provides a comprehensive analysis of various phytomolecules and their potential to target multiple aspects of AD pathology. We examined natural products from diverse classes, including stilbenes, flavonoids, phenolic acids, alkaloids, coumarins, terpenoids, chromenes, cannabinoids, chalcones, phloroglucinols, and polycyclic polyprenylated acylphloroglucinols (PPAPs). The key mechanisms of action of these phytomolecules include modulating tau protein dynamics to reduce aggregation, inhibiting acetylcholinesterase (AChE) to maintain neurotransmitter levels and enhance cognitive function, and inhibiting β-secretase (BACE1) to decrease Aβ production. Additionally, some phytomolecules were found to influence GSK-3β activity, thereby impacting tau phosphorylation and neurodegeneration. By addressing multiple targets, Aβ production, tau hyperphosphorylation, AChE activity, and GSK-3β, these natural products offer a promising multi-targeted approach to AD therapy. This review highlights their potential to develop effective treatments that not only mitigate core pathological features but also manage the complex, multifactorial aspects of AD progression.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117401"},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435379","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":"Exploring β-carboline hybrids and their derivatives: A review on synthesis and anticancer efficiency","authors":"Nur Fatihah Sulaiman ,&nbsp;Siti Zafirah Zulkifli ,&nbsp;Aimi Suhaily Saaidin ,&nbsp;Ravindar Lekkala ,&nbsp;Nurul Izzaty Hassan ,&nbsp;Noor Hidayah Pungot","doi":"10.1016/j.ejmech.2025.117412","DOIUrl":"10.1016/j.ejmech.2025.117412","url":null,"abstract":"<div><div>β-Carboline is a crucial compound in medicinal chemistry known for its versatile pharmacological activities. Recent research has focused on hybrid molecules incorporating a β-carboline scaffold linked to other pharmacophore moieties. These hybrid compounds have demonstrated diverse therapeutic properties, including anticancer, antianxiety, antimalarial, antidepressant, anti-inflammatory, antileishmanial, and antioxidant effects. This review highlights studies conducted from 2014 to the present with a particular emphasis on the development of β-carboline hybrid compounds and their derivatives as potent anticancer agents. The structure-activity relationship (SAR) analysis reveals that these hybrids exhibit significant cytotoxicity against various cancer cell lines. This review aims to inspire further research into the novel synthesis and evolution of β-carboline hybrids and their derivatives, potentially leading to new therapeutic advancements.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117412"},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435375","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 coumarin and procaine linked hybrid molecules as a novel class of SHP1 fluorescent activators","authors":"Xu-Yang Mu ,&nbsp;Li-Xin Gao ,&nbsp;Zhen-Xuan Zhang ,&nbsp;Zi-Tong Cao ,&nbsp;Qing Cao ,&nbsp;Chun Zhang ,&nbsp;Jia Li ,&nbsp;Da-Jun Xiang ,&nbsp;Yu-Bo Zhou ,&nbsp;Wen-Long Wang","doi":"10.1016/j.ejmech.2025.117394","DOIUrl":"10.1016/j.ejmech.2025.117394","url":null,"abstract":"<div><div>The development of small fluorescent organic molecules used in bioimaging experiment has boomed the progress of molecular and cellular biology, providing new and efficient tools to elucidate a myriad of cellular and multicellular processes. In this work, a class of fluorescent activators against SHP1 was designed and synthesized for the first time. The representative compound <strong>3n</strong> showed activating effect against SHP1 with EC₅₀ of 17.66 ± 1.48 μM and a fluorescence quantum yield of 0.521 in DMSO. Meanwhile, <strong>3n</strong> showed good selectivity for SHP1, inhibited the proliferation of SU-DHL-2 cells and OCI-Ly10 cells with IC₅₀ of 8.66 ± 1.26 μM and 9.16 ± 0.53 μM and exhibited potential for cellular imaging on human breast cancer cells.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117394"},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426964","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 Wnt inhibitor DK419: Reversing temozolomide resistance in glioblastoma by switching off Wnt/β-catenin signaling pathway to inhibit MGMT expression","authors":"Peiying Bai ,&nbsp;Peng Wang ,&nbsp;Ting Ren ,&nbsp;Qing Tang ,&nbsp;Na Zhang ,&nbsp;Lijiao Zhao ,&nbsp;Rugang Zhong ,&nbsp;Guohui Sun","doi":"10.1016/j.ejmech.2025.117411","DOIUrl":"10.1016/j.ejmech.2025.117411","url":null,"abstract":"<div><div>Temozolomide (TMZ) remains the primary oral chemotherapeutic agent for glioblastoma, but its efficacy is hampered by resistance mechanisms involving O⁶-methylguanine-DNA methyltransferase (MGMT). MGMT repairs the TMZ-induced lethal O⁶-methylguanine (O⁶-MeG) lesions, leading to treatment resistance. Current small molecule covalent MGMT inhibitors have limited clinical application due to severe hematological toxicity when used with TMZ. Therefore, alternative strategies to overcome MGMT-mediated resistance are critically needed. Targeting the Wnt/β-catenin signaling pathway to suppress MGMT expression presents a promising approach. We synthesized and discovered that a novel Wnt inhibitor, DK419 (6-chloro-2-(trifluoromethyl)-N-(4-(trifluoromethyl)phenyl)-1H -benzimidazole-4-carboxamide), effectively suppressed MGMT expression within 12 h in TMZ-resistant SF763 and SF767 cell lines. DK419 demonstrated synergistic cytotoxic effects with TMZ in these cell lines, while only an additive effect was observed in MGMT-negative SF126 cells. Furthermore, DK419 significantly enhanced TMZ's inhibitory effects on cell proliferation, colony formation, invasion, and migration, while also promoting apoptosis. In a resistant mouse tumor xenograft model, DK419 significantly boosted TMZ's tumor growth suppression, maintaining good biosafety. Western blot analysis revealed that DK419 markedly inhibited the nuclear translocation of β-catenin and decreased the expression of its downstream targets, Cyclin D1 and MGMT. The addition of the Wnt activator LiCl reversed DK419-induced effects on β-catenin nuclear translocation and Cyclin D1 and MGMT expression. For the first time, our findings demonstrate that DK419 can significantly enhance glioblastoma sensitivity to TMZ by modulating the Wnt/β-catenin pathway to downregulate MGMT expression.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117411"},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435376","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 potent quinone oxidoreductase 2 inhibitors to overcome TRAIL resistance of non-small cell lung cancer","authors":"Si-jie Qi ,&nbsp;Ke-xin Liu ,&nbsp;Hao-yu Liu ,&nbsp;Gao-qiang Zhang ,&nbsp;Hong-bo Zheng ,&nbsp;Jia-yu Sun ,&nbsp;Bin Sun ,&nbsp;Hong-xiang Lou","doi":"10.1016/j.ejmech.2025.117382","DOIUrl":"10.1016/j.ejmech.2025.117382","url":null,"abstract":"<div><div>Resistance to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) of cancer cells is a main obstacle for the chemotherapy. NRH: quinone oxidoreductase 2 (NQO2), known as a chemopreventive target, has emerged as a promising therapeutic target for overcoming TRAIL resistance in non-small cell lung cancer (NSCLC). Here we report the design, synthesis and evaluation of resveratrol analogues as novel selective NQO2 inhibitors, and analogue 20b, with potent NQO2 inhibitory activity (IC₅₀ = 95 nM) and relatively low cytotoxicity, displayed synergistic lethal effects in combination with TRAIL on TRAIL-resistant NSCLC cells. In addition, mechanistic studies revealed that <strong>20b</strong> sensitized TRAIL-resistant A549 cells to apoptosis through the generation of reactive oxygen species (ROS) and the upregulation of death receptor 5 (DR5). Furthermore, 20b showed no acute toxicity in the healthy mice at a single dose of 2000 mg/kg. Molecular docking confirmed the binding mode of 20b within the NQO2 active site, highlighting key interactions responsible for its enhanced potency. This study provided novel molecular templates for development of NQO2 inhibitor, and laid a foundation for developing agents against TRAIL-resistant cancers for targeting NQO2.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117382"},"PeriodicalIF":6.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426968","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":"A progress report in advancements of heterocyclic compounds as novel antimalarial agents over the last 5 years","authors":"Sumit Tahlan ,&nbsp;Sucheta Singh ,&nbsp;Meenakshi Kaira ,&nbsp;Hrithik Dey ,&nbsp;Kailash C. Pandey","doi":"10.1016/j.ejmech.2025.117393","DOIUrl":"10.1016/j.ejmech.2025.117393","url":null,"abstract":"<div><div>Malaria, caused by Plasmodium parasites and transmitted by Anopheles mosquitoes, remains a significant global health challenge, especially in tropical and subtropical regions where the disease is endemic. The complex Plasmodium lifecycle, involving stages in both the liver and bloodstream, leads to symptoms such as high fever, anemia, and, in severe cases, life-threatening complications, particularly <em>P. falciparum</em> infections. While historical treatments such as quinine and modern therapies such as artemisinin-based combination therapies (ACTs) have been effective, the growing issue of drug and insecticide resistance undermines these efforts. This resistance has spurred the need for new antimalarial drugs and strategies. Among the promising areas of research are heterocyclic compounds, which, due to their diverse and versatile chemical structures, are being investigated for their ability to disrupt the <em>Plasmodium</em> lifecycle. These compounds have potential as novel therapeutic agents that could enhance current treatment options. Understanding the mechanisms underlying drug resistance and advancing these therapeutic innovations are crucial for maintaining effective malaria control and treatment, highlighting the importance of on-going research in this field.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"289 ","pages":"Article 117393"},"PeriodicalIF":6.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418152","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}