European Journal of Medicinal Chemistry Reports最新文献

{"title":"Synthesis of novel derivatives from machilin C/D as antiproliferative agents against triple negative breast cancer","authors":"Alyson M. Ackerman ,&nbsp;Chibuzor Olewele ,&nbsp;Bert C. Lynn ,&nbsp;Samuel G. Awuah","doi":"10.1016/j.ejmcr.2025.100272","DOIUrl":"10.1016/j.ejmcr.2025.100272","url":null,"abstract":"<div><div>Lignans are small polyphenolic compounds that play an active role in plant defense against pathogens and predators. Recently, lignan machilin D was reported to be effective as an anti-tumorigenic agent in triple negative breast cancer (TNBC) tumor-bearing mice. Previous studies have relied on plant-extracted material limiting scalability and diversification of the natural scaffold. Herein, we describe a generalizable one-pot synthesis of machilin D and its derivatives via an iron chloride-induced dimerization of isoeugenol. Employing this synthetic methodology allowed for a robust diversification campaign to access seven (7) new lignan derivatives of the machilin D family with superior anti-proliferative properties in 2D and 3D TNBC models. Overall, this work enables lignan natural product-based drug discovery as a platform to identify new probes to elucidate lignan targets in biology and therapeutics for aggressive cancers such as TNBC.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100272"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring pyridinium-based inhibitors of cholinesterases: A review of synthesis, efficacy, and structural insights","authors":"Efraín Polo-Cuadrado ,&nbsp;Cristian Rojas-Peña ,&nbsp;Karen Acosta-Quiroga ,&nbsp;Lorena Camargo-Ayala ,&nbsp;Yeray A. Rodríguez-Núñez ,&nbsp;Edison Osorio ,&nbsp;Jhon J. López ,&nbsp;Rhonny Brid-Cuadrado ,&nbsp;Margarita Gutierrez","doi":"10.1016/j.ejmcr.2025.100270","DOIUrl":"10.1016/j.ejmcr.2025.100270","url":null,"abstract":"<div><div>Pyridinium-based compounds have emerged as promising multifunctional agents for Alzheimer's disease therapy, demonstrating remarkable dual inhibition of acetylcholinesterase and butyrylcholinesterase. This comprehensive analysis of more than 100 derivatives revealed that strategic structural modifications significantly enhance their therapeutic potential. Disubstituted analogues, representing more than half of the reported compounds, show particular promise, with many achieving exceptional potency below 100 nM, surpassing reference drugs such as donepezil, in optimized cases. Molecular Insights confirmed the presence of important interactions within the catalytic active site (CAS) and peripheral active site (PAS), explaining their robust inhibitory activity and highlighting several successful design approaches. Incorporating cationic groups at the 1,3-positions dramatically improves catalytic site binding, as seen in compounds such as Bb4, with an impressive 6.2 nM activity. Bulky aromatic extensions, such as naphthyl moieties, effectively target peripheral sites, while optimal C7-C12 linkers in bivalent structures enable the simultaneous engagement of both catalytic and peripheral sites. Planar fused-ring systems, particularly β-carboline derivatives, demonstrate enhanced blood-brain barrier penetration, which is a crucial challenge in CNS drug development. These compounds showed potential beyond cholinesterase inhibition, with selected derivatives exhibiting additional benefits against β-amyloid aggregation, oxidative stress, and NMDA) receptor modulation. However, their path to clinical application requires overcoming significant hurdles, particularly in demonstrating reliable blood-brain barrier penetration and establishing comprehensive safety profiles. Future progress depends on rigorous in vivo validation using disease-relevant models coupled with systematic optimization of pharmacokinetic properties. By addressing these challenges, pyridinium-based scaffolds could evolve into valuable multifunctional therapeutics, offering new hope for Alzheimer's patients through their unique combination of mechanisms and tunable chemical properties.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-stage functionalization of anticancer agent Daniquidone and the in vitro anticancer activities of the derivatives","authors":"Geshuyi Chen ,&nbsp;Yechun Zeng ,&nbsp;Xin Chen ,&nbsp;Zhe Chang ,&nbsp;Pei Yuan ,&nbsp;Haijia Chen ,&nbsp;Yongxiu Yang ,&nbsp;Xiaolei Liang ,&nbsp;Kun Yue ,&nbsp;Depeng Zhao","doi":"10.1016/j.ejmcr.2025.100269","DOIUrl":"10.1016/j.ejmcr.2025.100269","url":null,"abstract":"<div><div>Nitrogen heterocycles play an important role in drugs and natural products. C-H late-stage functionalization (LSF) of N-heterocycles might provide a direct route to construct diversified analogues with potential pharmaceutical activities. Here, we employed a Cu-catalyzed C–H LSF to modify an anticancer drug Daniquidone and successfully converted the N-α position C–H bond into C–O, C–C and C–S bonds. Anticancer activities of all modified compounds <em>in vitro</em> were measured against three cell lines. The results showed that compound <strong>2i</strong> was the most active compound among all derivatives synthesized (IC₅₀ = 2.14 ± 1.23 μM against OVCAR-3, IC₅₀ = 4.07 ± 1.09 μM against A2780), <strong>1b</strong>, <strong>1g</strong> and <strong>2j</strong> also exhibit increased activity compared to the parent drug Daniquidone. Besides, molecular docking simulations with <strong>1b</strong>, <strong>1g</strong> and <strong>2j</strong> were conducted to further understand their binding modes.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-based drug delivery for breast cancer treatment: Current applications and future directions","authors":"Md Abdus Samad ,&nbsp;Iftikhar Ahmad ,&nbsp;Torki A. Zughaibi ,&nbsp;Mohd Suhail ,&nbsp;Syed Kashif Zaidi ,&nbsp;Fahad A. Al-Abbasi ,&nbsp;Shams Tabrez","doi":"10.1016/j.ejmcr.2025.100268","DOIUrl":"10.1016/j.ejmcr.2025.100268","url":null,"abstract":"<div><div>Breast cancer (BC) is one of the most prevalent cancers in women worldwide. Limited specificity, systemic toxicity, risk of recurrence, and drug resistance are some of the drawbacks of traditional BC treatment approaches. Therefore, it is crucial to develop more effective, safe, and customized management plans for BC. The application of nanoparticle-based systems, such as liposomes, nanostructured lipid carriers, polymeric micelles, polymeric nanoparticles, dendrimers, and hybrid nanoparticles, has drawn significant interest in BC treatment. Nanomedicine can enhance the efficacy of drugs through active targeting, better tissue penetration, and more efficient tumor suppression <em>via</em> improved retention and permeability. Additionally, gene delivery using hybrid and theranostic nanomedicine has also been explored in BC treatment. Numerous nanomedicines have been used clinically for the treatment of breast cancer, some of which have already received U.S. Food and Drug Administration (USFDA) approval. Here, we focus on nanotechnology-based therapeutic approaches for BC treatment and highlighted their enhanced efficacy and reduced side effects. In addition, we have also explored on the possible utilization of Artificial Intelligence (AI) nanomedicine and bioinspired nanocarriers for BC treatment, which could pave the way for more precise, effective, and personalized therapies by improving nanoparticle design, optimizing drug delivery systems, and leveraging big data analytics.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zuogui Wan attenuates ovariectomy-induced osteoporosis via the GH/IGF1 axis and related pathways","authors":"Yujie Ma ,&nbsp;Pei Li ,&nbsp;Changheng Song ,&nbsp;Yuhan Wang ,&nbsp;Qiqi Yan ,&nbsp;Ying Yang ,&nbsp;Wenjie Li ,&nbsp;Xinyu Wan ,&nbsp;Ruyuan Zhu ,&nbsp;Jiayi Ma ,&nbsp;Yanjing Chen ,&nbsp;Haixia Liu ,&nbsp;Zhiguo Zhang","doi":"10.1016/j.ejmcr.2025.100264","DOIUrl":"10.1016/j.ejmcr.2025.100264","url":null,"abstract":"<div><h3>Introduction</h3><div>Zuogui Wan (ZGW)—one of the classic Chinese formulas—is clinically used to treat osteoporosis (OP). The current investigation aimed to analyze the phytochemical profile of ZGW and to elucidate its mechanisms of action in counteracting OP induced by ovariectomy (OVX) in rats.</div></div><div><h3>Methods</h3><div>The UPLC-MS/MS method was employed to determine the unique qualitative profile of the compounds. OVX rats were subjected to ZGW treatment for 12 weeks. Changes in body weight and bone protective effects were evaluated using various assays, including Vaginal smear assay, HE staining, Micro-CT imaging, and biomechanical testing. The related genes and proteins were validated using RT-qPCR, IHC, and Western blot.</div></div><div><h3>Results</h3><div>The UPLC-MS/MS analysis identified 2091 compounds, and the integral correction diagram showed 23 metabolites. ZGW treatment effectively ameliorated the diminished bone mineral density and compromised bone microstructures observed in OVX rats. Furthermore, ZGW administration to OVX rats increased bone tissue expression levels of RUNX2, BMP2, OSX, OC, and OPG. Moreover, ZGW administration in OVX rats restored the disturbed GH/IGF1 axis. Also, it activated PI3K/AKT signaling pathway and YAP/TAZ signaling pathway.</div></div><div><h3>Conclusion</h3><div>ZGW may exert its anti-OP effects by regulating the GH/IGF1 axis and its related signaling pathways.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incomplete functionalization of glycodendrimers: Effects on binding affinity with wheat germ agglutinin","authors":"Takahiko Matsushita ,&nbsp;Naomichi Toda ,&nbsp;Tetsuo Koyama ,&nbsp;Ken Hatano ,&nbsp;Koji Matsuoka","doi":"10.1016/j.ejmcr.2025.100266","DOIUrl":"10.1016/j.ejmcr.2025.100266","url":null,"abstract":"<div><div>Multivalent glycoconjugates are critical tools for elucidating lectin interactions and for designing inhibitors that target lectin-mediated biological processes. In this study, pentavalent <em>N</em>-acetylglucosamine (GlcNAc) carbosilane dendrimers (<strong>1a</strong>∼<strong>1c</strong>) were synthesized and efficiently isolated as intermediates during the production of hexavalent GlcNAc carbosilane dendrimers (<strong>2a</strong>∼<strong>2c</strong>) using recycling gel permeation chromatography. Although these pentavalent glycodendrimers were previously separable, they had not been thoroughly characterized. Here, their binding interactions with wheat germ agglutinin (WGA) were examined via fluorometric titration assays, revealing comparable binding affinities to those of their hexavalent counterparts. Statistical analysis further demonstrated significant differences in binding behavior between pentavalent and hexavalent glycodendrimers, as well as the effects of spacer length on lectin interactions. These findings show that partial glycosylation retains strong lectin-binding capacity and provide new insights into the interplay among valency, spacer length, and the overall architecture of glycodendrimers in glycan–lectin interactions.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,3,4-Oxadiazole-based EGFR inhibitors as anticancer therapeutics: SAR study and binding mode of interaction analysis","authors":"Ajeya Samanta ,&nbsp;Avik Maji ,&nbsp;Abhik Paul ,&nbsp;Sai Satyaprakash Mishra ,&nbsp;Sourin Nahar ,&nbsp;Tapan Kumar Maity","doi":"10.1016/j.ejmcr.2025.100265","DOIUrl":"10.1016/j.ejmcr.2025.100265","url":null,"abstract":"<div><div>In recent years, cancer has emerged as a significant challenge to the healthcare system, and medicinal researchers are tirelessly working to develop new potential medications to combat this disease. Despite the progress in the diagnosis of the pathophysiology of cancer and several treatment options, it is still the leading cause of death in the 21st century. Researchers have explored numerous molecular targets of cancer, including various protein kinases, phosphatases, and proteins regulating cell cycle and apoptosis. In the meantime, tyrosine kinases (TKs) have evolved as the key enzymes involved in the pathogenesis of solid tumours. Among them, EGFR or ErbB1 has been implicated in several cancers like cancer of the lungs, breast, cervical, liver, colorectal, etc. A fascinating approach to cancer treatment involves inhibiting the expression of EGFR or HER1 TK. The 1,3,4-oxadiazole scaffold is a crucial heterocycle that serves several medicinal roles, including cancer treatment. In the last decade, 1,3,4-oxadiazole hybrids have shown potential as anticancer agents by inhibiting EGFR expression and function. This study delves into the advancement of 1,3,4-oxadiazole-based EGFR inhibitors with SAR studies and their binding mode of interaction analysis. Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with 1,3,4-oxadiazole-based EGFR inhibitors for anti-cancer action.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanostructures: An efficient drug delivery platform for therapy of multiple myeloma","authors":"Teodora Eliana Petcov ,&nbsp;Vadim V. Silberschmidt ,&nbsp;Mădălina Andreea Pandele ,&nbsp;Elena Alina Chiticaru ,&nbsp;Mariana Ioniță ,&nbsp;Marius Manole","doi":"10.1016/j.ejmcr.2025.100263","DOIUrl":"10.1016/j.ejmcr.2025.100263","url":null,"abstract":"<div><div>Recent advancements in the biomedical field, particularly in drug delivery technologies, have paved the way for novel approaches to the diagnosis and treatment of multiple myeloma, a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. Conventional treatments often fail to provide long-term efficacy, leading to a need for more effective therapies. Nanoscale drug delivery platforms demonstrated their potential to facilitate superior drug targeting, reduce systemic toxicity, and enhance therapeutic efficacy by inhibiting the growth of tumor cells. This review aims to highlight the most important features of the nanostructures used for drug delivery and recent advances in several nanostructures, including liposomes, micelles, polymeric and inorganic nanoparticles, carbon-based nanostructures, DNA nanostructures for multiple myeloma, as well as quantum dots, and nanocomposites used to deliver the chemotherapeutic agents. Furthermore, it evaluates the efficacy and mechanisms of internalization of nanostructures as controlled delivery systems for anticancer drugs in the treatment of multiple myeloma. The current review goes one step further to elucidate the potential of nanotechnology to revolutionize multiple myeloma therapy through targeted drug delivery systems based on various nanostructures.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100263"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation in the CB1 and CB2 receptor binding profile and intrinsic activity of (−) and (+)-enantiomers of some naturally occurring phytocannabinoids or synthetic derivatives","authors":"Santiago Rodríguez-Carreiro ,&nbsp;María Gómez-Cañas ,&nbsp;Francesca Lubrini ,&nbsp;Claudia Gonzalo-Consuegra ,&nbsp;Matthias Winkler ,&nbsp;Diego Caprioglio ,&nbsp;Giovanni Appendino ,&nbsp;Concepción García ,&nbsp;Paula Morales ,&nbsp;Nadine Jagerovic ,&nbsp;Joerg T. Fischer ,&nbsp;Bernd L. Fiebich ,&nbsp;Marcus R. Goetz ,&nbsp;Eduardo Muñoz ,&nbsp;Javier Fernández-Ruiz","doi":"10.1016/j.ejmcr.2025.100262","DOIUrl":"10.1016/j.ejmcr.2025.100262","url":null,"abstract":"<div><div>Cannabidiol (CBD) and cannabidivarin (CBDV) have shown promising clinical efficacy for the management of epilepsy, and beneficial effects have been demonstrated for CBD in a diversity of other pathologies (pain, schizophrenia, Tourette syndrome, anxiety). However, the mechanism(s) involved are still largely elusive, as are the molecular target(s) involved. CBD and CBDV do not orthosterically bind the cannabinoid type-1 (CB₁) and type-2 (CB₂) receptors, showing only modest allosteric modulation of both end-points. CBD and CBDV are biosynthesized as optically highly pure (−)-enantiomers, and most bioactivity data refer to these forms. (+)-CBD and related analogues [(+)-cannabidiolic acid (CBDA), its esters, and (+)-CBDV] can be obtained by chemical synthesis, and we present evidence that the (+)- and (−)-enantiomers of CBD, CBDV and of a selection of derivatives of CBDA have distinct binding profiles and functional activity at the CB₁/CB₂ receptors. Thus, with the single exception of the methyl ester of CBDA, all the (+)-enantiomers showed higher affinities than the (−)-isomers for both receptors, in particular for the CB₂ receptors. The affinity of the (+)-enantiomers for both CB₁ and CB₂ receptors showed a marked dependence on the nature of the alkyl residue on the aromatic ring and the esterification pattern of CBDA. Potency was rarely in the low nM value for CB₁, but generally so for CB₂. Enantiomers showing low nM activity were further investigated for their intrinsic activity using GTPγS binding assays. This proved that (+)-CBD, (+)-CBDV and the methyl ester of (+)-CBDA are agonists at the CB₂ receptor, with the β-hydroxyethyl ester of (+)-CBDA being an inverse agonist, and its β-hydroxypentyl ester behaving as an agonist at CB₁ and an inverse agonist at CB₂. Finally, we assayed <em>in vitro</em> the anti-inflammatory and neuroprotective properties of three compounds [(+)-CBD, (+)-CBDV and (+)-CBDA methyl ester] strongly activating CB₂, showing their ability to reduce the production of proinflammatory factors and protecting neurons against their toxicity. Remarkably, these benefits were eliminated by the selective blockade of the CB₂ receptor, highlighting its role as a (+)-CBD target. In summary, our data show that remarkable differences between (−)- and (+)-enantiomers of CBD, CBDV and related compounds exist in terms of CB₁/CB₂ receptor binding profile and intrinsic activity. The observation that the natural (−)-enantiomers do not bind CB₂ receptors suggests that their effects are associated with different targets.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100262"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzo[b]thiophene-based 5-lipoxygenase inhibitors: A comprehensive review of therapeutic advances","authors":"Muhammed Jamshad Kongath ,&nbsp;Ameena Salim","doi":"10.1016/j.ejmcr.2025.100261","DOIUrl":"10.1016/j.ejmcr.2025.100261","url":null,"abstract":"<div><div>Heterocyclic compounds have an irreplaceable position in medicinal chemistry. Almost all bioactive natural products have heteroatoms in their active components. Benzo[b]thiophene is one of the important compounds among them. Several drugs contain benzo[b]thiophene as a potential portion responsible for pharmacological action. Zileuton, a potential 5-LOX inhibitor, is such a compound, having a benzo[b]thiophene ring as a crucial structural feature. Some of the previous research works revealed that a major side effect of zileuton is hepatotoxicity, which is found to be due to the presence of N-hydroxyurea attached to the benzo[b]thiophene ring. In this review article, we performed a systematic review of previous works for structural modification on the benzo[b]thiophene ring to improve its biological activity against the 5-LOX enzyme. Also, we compared the structure and biological activity and conducted a brief study of the structural activity relationship of the benzo[b]thiophene ring against the 5-LOX enzyme. Finally, we concluded that some positions of the benzo[b]thiophene ring are literally prone to an increase in 5-LOX inhibition after substituting with privileged motifs. So, substitution on the benzo[b]thiophene ring is able to develop much better 5-LOX inhibitors in the future.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}