European Journal of Medicinal Chemistry最新文献_第9页

Discovery and optimization of tetrahydroacridine derivatives as a novel class of antibiotics against multidrug-resistant Gram-positive pathogens by targeting type I signal peptidase and disrupting bacterial membrane 发现并优化四氢吖啶衍生物，将其作为一种新型抗生素，通过靶向 I 型信号肽酶和破坏细菌膜来抗击具有多重耐药性的革兰氏阳性病原体

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-26 DOI: 10.1016/j.ejmech.2024.117101

Xiaolin Lu , Xianghan Xu , Yushi Ding , Xin Gong , Liqin Ming , Xingyang Dai , Congying Gu , Jiayi Wang , Jiaqi Zhao , Mengkang Gao , Hao Yin , Zhi Wang , Xiaoming Wang , Liping Wang , Dayong Zhang , Menghan Zhang , Jinhu Huang

{"title":"Discovery and optimization of tetrahydroacridine derivatives as a novel class of antibiotics against multidrug-resistant Gram-positive pathogens by targeting type I signal peptidase and disrupting bacterial membrane","authors":"Xiaolin Lu , Xianghan Xu , Yushi Ding , Xin Gong , Liqin Ming , Xingyang Dai , Congying Gu , Jiayi Wang , Jiaqi Zhao , Mengkang Gao , Hao Yin , Zhi Wang , Xiaoming Wang , Liping Wang , Dayong Zhang , Menghan Zhang , Jinhu Huang","doi":"10.1016/j.ejmech.2024.117101","DOIUrl":"10.1016/j.ejmech.2024.117101","url":null,"abstract":"<div><div>Increasing antimicrobial resistance underscores the urgent need for new antibiotics with unique mechanisms. Type I signal peptidase (SPase I) is crucial for bacterial survival and a promising target for antibiotics. Herein we designed and synthesized innovative tetrahydroacridine-9-carboxylic acid derivatives by optimizing the initial hit compound <strong>SP11</strong> based on virtual screening. Structure-activity relationship (SAR) studies and bioactivity assessments identified compound <strong>C09</strong> as a standout, showing excellent <em>in vitro</em> antimicrobial activity against MRSA and other multidrug-resistant Gram-positive pathogens. <strong>C09</strong> targets SPase I with a favorable affinity, disrupts bacterial cell membranes, and eradicates biofilms, reducing resistance risk. <em>In vivo</em> tests in a murine MRSA skin infection model demonstrated significant efficacy. Additionally, <strong>C09</strong> has good liver microsome metabolic stability, safe hemolytic activity and mammalian cytotoxicity, as well as a good <em>in vivo</em> safety profile. Overall, our findings highlight the potential of tetrahydroacridine-9-carboxylic acid derivatives as a novel class of antibiotics against multidrug-resistant Gram-positive bacteria.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117101"},"PeriodicalIF":6.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719045","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}

引用次数: 0

PRMT7 in cancer: Structure, effects, and therapeutic potentials 癌症中的 PRMT7：结构、作用和治疗潜力

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-26 DOI: 10.1016/j.ejmech.2024.117103

Guan-Jun Yang , Yan-Jun Liu , Ru-Yi Chen , Jin-Jin Shi , Chang-Yun Li , Ran Wang , Jing Yu , Jian-Fei Lu , Le-Le Zhang , Bin Yu , Jiong Chen

引用次数: 0

Design and functional studies of xylene-based cyclic mimetics of SOCS1 protein 二甲苯基 SOCS1 蛋白环状模拟物的设计与功能研究

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-25 DOI: 10.1016/j.ejmech.2024.117107

Alessia Cugudda , Sara La Manna , Marilisa Leone , Marian Vincenzi , Daniela Marasco

{"title":"Design and functional studies of xylene-based cyclic mimetics of SOCS1 protein","authors":"Alessia Cugudda , Sara La Manna , Marilisa Leone , Marian Vincenzi , Daniela Marasco","doi":"10.1016/j.ejmech.2024.117107","DOIUrl":"10.1016/j.ejmech.2024.117107","url":null,"abstract":"<div><div>Peptidomimetics of Suppressors of cytokine signaling 1 (SOCS1) protein demonstrated valid therapeutic potentials as anti-inflammatory agents. Indeed, SOCS1 has a small kinase inhibitory region (KIR) primarily involved in the inhibition of the JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway Herein, on the basis of previous investigations on a potent mimetic of KIR-SOCS1, named PS5, we designed and evaluated the SAR (Structure Activity Relationship) features of two xylene-based macrocycles analogues of PS5. These novel compounds bear thiol-xylene linkages with mono- and bi-cyclic scaffolds: they were <em>in vitro</em> functionally investigated toward JAK2 catalytic domain, as ligands with microscale thermophoresis (MST) and as inhibitors through LC-MS analyses. To evaluate structural properties Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopies were employed along with serum stability assays. Results indicated that a monocycle scaffold is well-tolerated by PS5 sequence enhancing the affinity toward the kinase with a K<sub>D</sub> in the low micromolar range and providing consistent inhibitory effects of the catalytic activity, which were evaluated for the first time in the case of SOCS1 mimetics. Conformationally, the presence of xylene scaffold affects the flexibility of the compounds and their stabilities to proteases degradation. This study contributes to the understanding of the factors necessary for accurately mimicking the inhibitory mechanism of SOCS1 protein towards JAK2 and to the translation of proteomimetics into drugs.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117107"},"PeriodicalIF":6.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696775","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}

引用次数: 0

Recent advances in screening methods enabling the discovery of novel anti-hepatitis B virus drug candidates 有助于发现新型抗乙型肝炎病毒候选药物的筛选方法的最新进展

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-25 DOI: 10.1016/j.ejmech.2024.117093

Yu Jin, Shuo Wang, Kai Tang, Peng Zhan, Xinyong Liu

{"title":"Recent advances in screening methods enabling the discovery of novel anti-hepatitis B virus drug candidates","authors":"Yu Jin, Shuo Wang, Kai Tang, Peng Zhan, Xinyong Liu","doi":"10.1016/j.ejmech.2024.117093","DOIUrl":"10.1016/j.ejmech.2024.117093","url":null,"abstract":"<div><div>The global population affected by Hepatitis B virus (HBV) is approximately 296 million, but few drugs have been able to completely eradicate HBV and the range of effective treatments remains limited. Recent advancements in molecular biology and artificial intelligence, as well as a comprehensive understanding of the molecular structure of HBV, have greatly aided the rational development of anti-HBV agents. Such advancements have facilitated an increasing array of candidate drugs transitioning into clinical trials, however, no novel target-based compounds have been approved for clinical application. To expedite the progression of anti-HBV drug development, establishing a reliable and robust <em>in vitro</em> HBV infection system is of great importance. However, owing to the host and tissue specificity of HBV, identifying a stable and dependable cell culture system for screening all anti-HBV agents poses significant challenges. In this review, we summarize recent advances in screening methods for small-molecule inhibitors that target key stages of the HBV replication cycle from a medicinal chemistry perspective.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117093"},"PeriodicalIF":6.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696739","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}

引用次数: 0

Mitochondria-targeting artesunate-rhein conjugates: Linker-modulated cell-permeability, heme-affinity and anticancer activity 线粒体靶向青蒿琥酯-血红素共轭物：连接体调节的细胞渗透性、血红素亲和力和抗癌活性

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-24 DOI: 10.1016/j.ejmech.2024.117100

Dan-Dan Wang , Li He , Ming-Hui Qi , Hong-Yang Zhao , Ai-Xi Yu , Shi-Wen Huang

{"title":"Mitochondria-targeting artesunate-rhein conjugates: Linker-modulated cell-permeability, heme-affinity and anticancer activity","authors":"Dan-Dan Wang , Li He , Ming-Hui Qi , Hong-Yang Zhao , Ai-Xi Yu , Shi-Wen Huang","doi":"10.1016/j.ejmech.2024.117100","DOIUrl":"10.1016/j.ejmech.2024.117100","url":null,"abstract":"<div><div>Heme, abundant in the mitochondria of cancer cells, is a key target for the anticancer activity of artemisinin (ART). Current strategies to enhance the anticancer activity of ART focus solely on its delivery to heme-enriched subcellular localizations while overlooking the decisive effects of ART-heme interactions. Here, we propose an ingenious strategy that synergizes mitochondria-targeted drug delivery and linker-mediated drug conformation modulation, thereby significantly enhancing the anticancer activity of ART. By strategically conjugating artemisinin (ART) with the mitochondria-targeting rhein (R) using different linkers, we aimed to precisely adjust the conformation of the conjugates. Comprehensive computational analysis revealed that the conjugate with the optimal linker length (C<sub>4</sub>) displayed a favorable conformation that facilitated cell permeability and exhibited the highest binding affinity to heme and Fe ions. Moreover, it exhibited superior tumor suppression capabilities both in vitro and in vivo, overcoming the uncertainty of in vivo application caused by the rapid clearance of the conventional mitochondria-targeted cation TPP<sup>+</sup>, and even inducing immunogenic cell death associated with immunotherapy. This novel strategy opens up a new avenue for the development of drug conjugate systems.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117100"},"PeriodicalIF":6.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694298","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}

引用次数: 0

Chemical probes for the identification of the molecular targets of honokiol 用于鉴定霍诺喹分子靶点的化学探针

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-24 DOI: 10.1016/j.ejmech.2024.117102

Henar Vázquez-Villa , Ainoa Rueda-Zubiaurre , Daniel Fernández , Román Foronda , Christopher G. Parker , Benjamin F. Cravatt , Mar Martín-Fontecha , Silvia Ortega-Gutiérrez

{"title":"Chemical probes for the identification of the molecular targets of honokiol","authors":"Henar Vázquez-Villa , Ainoa Rueda-Zubiaurre , Daniel Fernández , Román Foronda , Christopher G. Parker , Benjamin F. Cravatt , Mar Martín-Fontecha , Silvia Ortega-Gutiérrez","doi":"10.1016/j.ejmech.2024.117102","DOIUrl":"10.1016/j.ejmech.2024.117102","url":null,"abstract":"<div><div>Honokiol is a natural product with an interesting array of biological effects, including significant anti-tumor properties. However, full exploration of its therapeutic potential is hampered by its modest pharmacokinetic profile and by the lack of synthetic methods that allow to obtain specifically designed derivatives with improved properties. In addition, the specific molecular targets of honokiol remain poorly understood, a fact that limits the search of alternative hits for subsequent optimization programs. In this work we describe an optimized series of synthetic routes that allow to access to a variety of honokiol derivatives, including a set of minimalist photoaffinity probes to map potential protein targets in live cells. Chemical proteomic studies of the most potent probe revealed a defined set of proteins as the cellular targets of honokiol. Significantly, up to the 62 % of the identified proteins have described roles in cancer, highlighting their potential relationship with the antitumor effects of honokiol. Furthermore, several of the top hits have been validated as direct binding partners of honokiol by cellular thermal shift assay (CETSA). In sum, the work described herein provides the first landscape of the cellular targets of honokiol in living cells and contributes to define the specific molecular pathways affected by this natural product.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117102"},"PeriodicalIF":6.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694300","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}

引用次数: 0

Photosensitizer formulations in photodynamic therapy of age-related macular degeneration 老年黄斑变性光动力疗法中的光敏剂配方

IF 6.7 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-24 DOI: 10.1016/j.ejmech.2024.117105

Sandra Beirão, Patrícia M.R. Pereira, Rosa Fernandes, João P.C. Tomé

{"title":"Photosensitizer formulations in photodynamic therapy of age-related macular degeneration","authors":"Sandra Beirão, Patrícia M.R. Pereira, Rosa Fernandes, João P.C. Tomé","doi":"10.1016/j.ejmech.2024.117105","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117105","url":null,"abstract":"Age-related macular degeneration (AMD) is a progressive degenerative disease that leads to visual impairment, predominantly affecting the elderly. Despite significant advancements in treatment, a definitive cure remains elusive. Current therapeutic strategies only slow down disease progression, inhibiting abnormal blood vessels growth, and preserving or improving vision. Among these strategies, photodynamic therapy (PDT) has emerged as a promising treatment, particularly for neovascular form, the most severe form of the disease. Although several photosensitizers (PS) have been developed, only one has received clinical approval for use in AMD. This treatment involves the intravenous administration of a photosensitizing agent that preferentially accumulates in the abnormal blood vessels beneath the macula. Upon activation by targeted laser light, the PS triggers photochemical reactions, leading to vascular occlusion and the reduction of choroidal neovascularization. This review provides a comprehensive overview of both experimental and clinical studies on PDT for AMD, discussing the current state of research, challenges in treatment optimization, and potential future directions to enhance this therapeutic approach.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"18 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694297","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}

引用次数: 0

Design and synthesis of novel derivatives of bisepoxylignans as potent anti-inflammatory agents involves the modulation of the M1/M2 microglia phenotype via TLR4/NF-κB signaling pathway 通过TLR4/NF-κB信号通路调节M1/M2小胶质细胞表型，设计和合成新型双环氧木脂素衍生物作为强效抗炎剂

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-23 DOI: 10.1016/j.ejmech.2024.117092

Liang Xiong , Huilin Zhu , Jie Liu , Rongtao Wang , Ting Zhong , Xiaowen Jiang , Lei Tang , Yanhua Fan

{"title":"Design and synthesis of novel derivatives of bisepoxylignans as potent anti-inflammatory agents involves the modulation of the M1/M2 microglia phenotype via TLR4/NF-κB signaling pathway","authors":"Liang Xiong , Huilin Zhu , Jie Liu , Rongtao Wang , Ting Zhong , Xiaowen Jiang , Lei Tang , Yanhua Fan","doi":"10.1016/j.ejmech.2024.117092","DOIUrl":"10.1016/j.ejmech.2024.117092","url":null,"abstract":"<div><div>Bisepoxylignans have been reported to possess a variety of biological functions, especially in anti-inflammatory aspects. However, the bis-tetrahydrofuran scaffold restricts the type and position of substituents, which further limits the further optimization of their biological activity and druggability. Here, a series of novel derivative s of bisepoxylignans bearing 7<em>H</em>-pyrrolo[2,3-<em>d</em>]pyrimidin-4-amine and 1<em>H</em>-pyrazolo[3,4-<em>d</em>]pyrimidin-4-amine scaffolds were designed and synthesized by a scaffold hopping strategy. Biological evaluation demonstrated that compound <strong>7x</strong> exhibited the most potent anti-inflammatory activity, both <em>in vitro</em> and <em>in vivo</em>. Additionally, <strong>7x</strong> displayed an excellent oral safety profile at a dose of 500 mg/kg. The anti-inflammatory effect of <strong>7x</strong> is potentially mediated by the inhibition of the TLR4/NF-<em>κ</em>B pathway and the promotion of M1 to M2 microglial phenotypic conversion. Taken together, <strong>7x</strong> could be a promising lead compound for the development of novel therapeutic agents for the treatment of inflammatory diseases.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117092"},"PeriodicalIF":6.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694299","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}

引用次数: 0

In silico inspired design of urea noscapine congeners as anticancer agents: Chemical synthesis and experimental evaluation using breast cancer cells and a xenograft mouse model 在硅学启发下设计作为抗癌剂的尿苷元同系物：利用乳腺癌细胞和异种移植小鼠模型进行化学合成和实验评估

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-23 DOI: 10.1016/j.ejmech.2024.117091

Pratyush Pragyandipta , Eeshara Naik , Praveen Kumar Reddy , Arnab Nayek , Srinivas Kantevari , Pradeep K. Naik

{"title":"In silico inspired design of urea noscapine congeners as anticancer agents: Chemical synthesis and experimental evaluation using breast cancer cells and a xenograft mouse model","authors":"Pratyush Pragyandipta , Eeshara Naik , Praveen Kumar Reddy , Arnab Nayek , Srinivas Kantevari , Pradeep K. Naik","doi":"10.1016/j.ejmech.2024.117091","DOIUrl":"10.1016/j.ejmech.2024.117091","url":null,"abstract":"<div><div>A series of semisynthetic noscapine-urea congeners (<strong>7a-7h)</strong> as potential tubulin-binding agents are being developed by integrating a urea pharmacophore at the C-9 position of the noscapine scaffold. Their binding affinity to tubulin was predicted through molecular docking, molecular dynamics (MD) simulations, and the MM-PBSA approach. These molecules were subsequently chemically synthesized and assessed using breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human embryonic kidney cells (HEK). Both the docking score and the predicted binding free energy (<em>ΔG</em><sub><em>bind,pred</em></sub><em>)</em> revealed that urea congeners had a stronger affinity towards tubulin than noscapine and effectively inhibited the proliferation of all cancer cell types without affecting normal healthy cells. The results indicated that compound <strong>7g</strong> exhibited the most promise and was chosen for further studies. Moreover, MDA-MB-231 cells treated with <strong>7g</strong> at its IC<sub>50</sub> concentration showed morphological changes such as membrane blebbing, fragmented nuclei, and the presence of apoptotic bodies. Apoptosis induction was further confirmed by flow cytometry. Moreover, the tubulin binding assay revealed a greater binding affinity with an equilibrium dissociation constant (KD) of 42 ± 2.4 μM for compound <strong>7g</strong>. The number of MCF-7 cells engrafted as breast tumors in nude mice was found to be reduced significantly without any adverse effects. Noscapine is already in clinical trials, but the urea noscapine congener offers an advantage because of its increased potency without impacting the nontoxic profile of noscapine.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117091"},"PeriodicalIF":6.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694389","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}

引用次数: 0

Exploring the anticancer potential and mechanisms of action of natural coumarins and isocoumarins 探索天然香豆素和异香豆素的抗癌潜力和作用机制

IF 6 2区医学

European Journal of Medicinal Chemistry Pub Date : 2024-11-22 DOI: 10.1016/j.ejmech.2024.117088

Mohd Aqib , Shahnaaz Khatoon , Mujahid Ali , Shabana Sajid , Mohammed Ali Assiri , Shakir Ahamad , Mohammad Saquib , Mohd Kamil Hussain

{"title":"Exploring the anticancer potential and mechanisms of action of natural coumarins and isocoumarins","authors":"Mohd Aqib , Shahnaaz Khatoon , Mujahid Ali , Shabana Sajid , Mohammed Ali Assiri , Shakir Ahamad , Mohammad Saquib , Mohd Kamil Hussain","doi":"10.1016/j.ejmech.2024.117088","DOIUrl":"10.1016/j.ejmech.2024.117088","url":null,"abstract":"<div><div>Natural coumarins and isocoumarins show significant therapeutic potential against cancer in preclinical studies by targeting multiple pathways and processes<strong>.</strong> These compounds influence several critical cellular processes, such as apoptosis, autophagy, and cell cycle regulation, which are pivotal in cancer development and progression. Their capability to target multiple signalling pathways provides a strategic advantage over single-target therapies, which are often limited by drug resistance. Notably, coumarins have the potential to inhibit angiogenesis, the process through which tumours develop new blood vessels, thereby potentially restricting tumour growth and metastasis. Additionally, coumarins may enhance anticancer effects by modulating immune responses and reducing inflammation, thus offering a dual approach to combating cancer. They also show promise in addressing multidrug resistance, a significant challenge in cancer therapy, by targeting drug efflux proteins and potentially improving the efficacy of existing treatments. While preclinical studies are promising, further research is required to elucidate the pharmacokinetics, toxicity, and potential side effects of coumarins in humans. Continued clinical evaluation will be crucial to confirm their effectiveness in cancer patients. Nonetheless, their ability to target multiple pathways positions coumarin based molecules as potential candidates for future anti-cancer drug development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117088"},"PeriodicalIF":6.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684649","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}

引用次数: 0