European Journal of Medicinal Chemistry Reports最新文献

{"title":"Structure optimization at position five of 4-thiazolidinone resulted in new potent PIM1 kinase inhibitors with apoptosis induction and caspase 3/7 activation capabilities for combating colorectal cancer","authors":"Ahmed K. Al-Kubeisi ,&nbsp;Saad R. El-Zemity ,&nbsp;Marwa M. Abu-Serie ,&nbsp;Aly A. Hazzaa ,&nbsp;Mostafa M.M. El-Miligy","doi":"10.1016/j.ejmcr.2025.100279","DOIUrl":"10.1016/j.ejmcr.2025.100279","url":null,"abstract":"<div><div>New thymol – 5-phenylthiazolidin-4-one hybrids were synthesized aiming to interact with the lipophilic flexible p-loop of PIM kinase active site via induced-fit binding mode to increase affinity hence anticancer activity against colorectal cancer (CRC). All target compounds were screened for their cytotoxicity against normal human lung fibroblasts and anticancer activity against CRC Caco-2 cell lines. <strong>6c</strong> and <strong>6e</strong> exhibited the highest anticancer activity at doses less than their EC₁₀₀ on normal human cells. In addition, <strong>6c</strong> and <strong>6e</strong> were further tested against liver cancer cell line (HepG-2) and breast cancer cell line (MCF-7) and proved their potent anticancer activities. Furthermore, both induced apoptosis in Caco-2 cell lines by 39 and 55 % and enhanced caspase 3/7 activation by 43 and 65 %, respectively. Besides, <strong>6c</strong> and <strong>6e</strong> revealed <em>in vitro</em> inhibitory activity against PIM1 kinase more than PIM2 kinase. Furthermore, induced fit docking and molecular dynamics simulation of <strong>6c</strong> and <strong>6e</strong> predicted enhanced PIM1 kinase activity via interaction to flexible p-loop. Moreover, both could act as PIM1 kinase competitive non-ATP mimetics as they interacted with Lys67.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231741","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":"Towards \"unmakable\" psychedelics: SAR exploration of psilocin analogs obtained by a HATU-mediated amide coupling strategy","authors":"Judith Stirn ,&nbsp;Raphael Berger ,&nbsp;Harald Hübner ,&nbsp;Peter Gmeiner ,&nbsp;Christian D. Klein","doi":"10.1016/j.ejmcr.2025.100278","DOIUrl":"10.1016/j.ejmcr.2025.100278","url":null,"abstract":"<div><div>4-Hydroxytryptamines such as psilocin and its prodrug psilocybin are of considerable current interest for innovative antidepressant and other neuropsychiatric treatments. We here present a synthetic route towards 4-hydroxytryptamines displaying a high versatility for SAR exploration at the aliphatic nitrogen. The core concept is to apply HATU-mediated amide couplings to a readily accessible and stable <em>N</em>^<em>1</em>-Boc-indole-3-glyoxylic acid precursor followed by <em>N</em>-deprotection under mild conditions. We illustrate the versatility of this approach by the synthesis of various sterically hindered, conformationally constrained, chiral, and electron-deficient 4-hydroxytryptamines, including closely related congeners of iprocin. In addition, the structure-activity relationships of the obtained compounds are explored with a focus on their interaction with the serotonin receptors 1A and 2A (5-HT_1/2A). An increase in steric bulk at the aliphatic nitrogen appears to be detrimental to the affinity to the 5-HT_2A receptor, whereas azetidinyl tryptamines bearing a terminal aryl moiety demonstrated remarkably high affinity.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231740","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":"Isolation, synthesis, mechanism of action, and pharmacological activities of bisabolangelone and related bisabolenoids","authors":"Christian Bailly","doi":"10.1016/j.ejmcr.2025.100277","DOIUrl":"10.1016/j.ejmcr.2025.100277","url":null,"abstract":"<div><div>The bisabolene-type sesquiterpene bisabolangelone (BBG) can be found in several <em>Angelica</em> species, notably in the seeds of <em>A. silvestris</em> L. from which it was first isolated. BBG can be extracted from those plants or obtained by total synthesis from the monoterpenoid pulegone. Efficient procedures have been proposed to synthesize BBG and derivatives. The present review discusses the origin, bio- and chemical syntheses, and pharmacological properties of BBG. Three main activities have been reported, corresponding to three study periods. Initially, BBG was investigated as an insecticide active against <em>Dermatophagoides</em> (house dust mites) and a few other pest species. Later, the compound revealed marked hypopigmenting and anti-melanogenic activities of potential interest to treat hyperpigmented skin lesions. BBG was shown to competitively inhibit cAMP binding to the regulatory subunit of protein kinase A, to alter the functioning of transcription factors CREB and SOX9 implicated in melanogenesis. More recently, BBG was found to inhibit gastric H⁺/K⁺-ATPase, presumably via a direct binding to a site on the luminal surface of the proton pump. This mechanism of action, coupled with the antioxidant and anti-inflammatory effects, stimulated the design of more stable anti-ulcer BBG analogues with a reinforced H⁺/K⁺-ATPase inhibitory activity, such as oxime and hydrazone carboxamide derivatives. The better knowledge of the bioactivities and the mechanism of action of BBG should encourage studies of natural products with a similar scaffold, such as paniculides A-D, liginvolones A-D, osterivolones A-D, ashitabaol A and other bisabolenoids. Altogether, the review provides a complete survey of the chemistry and pharmacology of bisabolangelone to shed light on its potential therapeutic interest.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138211","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":"Reversing TGF-β1-induced fibrotic phenotype in human lung fibroblasts using a PROTAC tool derived from an indoline-based HDAC6 inhibitor","authors":"Ilaria Cursaro ,&nbsp;Valerio Ciccone ,&nbsp;Valeria Tudino ,&nbsp;Chiara Papulino ,&nbsp;Laura Scalvini ,&nbsp;Sandra Donnini ,&nbsp;Lucia Morbidelli ,&nbsp;Luca Bini ,&nbsp;Claudia Landi ,&nbsp;Chiara Contri ,&nbsp;Silvia Pasquini ,&nbsp;Fabrizio Vincenzi ,&nbsp;Katia Varani ,&nbsp;Alessio Lodola ,&nbsp;Marco Mor ,&nbsp;Rosaria Benedetti ,&nbsp;Lucia Altucci ,&nbsp;Stefania Butini ,&nbsp;Gabriele Carullo ,&nbsp;Sandra Gemma ,&nbsp;Giuseppe Campiani","doi":"10.1016/j.ejmcr.2025.100276","DOIUrl":"10.1016/j.ejmcr.2025.100276","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating interstitial lung disease characterized by limited therapeutic options, with only two FDA-approved palliative agents currently available. Given its poor prognosis and the high incidence of lung transplantation, there is a pressing need to develop innovative and effective therapeutics. Histone deacetylase 6 (HDAC6) has been identified as a key driver of fibrotic progression in IPF, and selective inhibitors of this isoform were able to revert the fibrotic phenotypes. Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that can trigger the degradation of a specific target in cells, including HDAC6 enzyme. Therefore, the application of PROTAC technology may represent a novel therapeutic strategy for IPF. We showcase the design, synthesis, and biological evaluation of a library of first-in-class antifibrotic HDAC6-targeting PROTACs, incorporating our <em>in-house</em> inhibitor <strong>1</strong> as the HDAC6 ligand. Newly developed PROTACs <strong>5a</strong> and <strong>5c</strong> showed effective degradation of HDAC6 in A549 lung cells and IMR-90 lung fibroblasts. <strong>5a</strong> and <strong>5c</strong> exhibited significant antifibrotic effects against the TGF-β1 induced fibrotic phenotype on IMR-90 cells, a model that mimics IPF conditions. The generation of putative ternary complexes involving PROTAC molecules, the E3-ligase cereblon (CRBN) and the HDAC6 target protein was supported by molecular modelling techniques, including protein-protein docking and molecular dynamics simulations. Mechanistic investigations, based on pull-down experiments, confirmed that the newly synthetized compounds were able to reduce HDAC6 levels through a proteasome- and CRBN-dependent mechanism as confirmed by experiments with neddylation and proteasome inhibitors. This pioneering exploration of targeted protein degradation in IPF-like conditions provides compelling evidence of its therapeutic promise, paving the way for a broader application of PROTACs in treating rare diseases.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134767","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":"Mitochondria-targeting phosphonium salts of monensin A as the source of novel antiproliferative agents","authors":"Michał Sulik ,&nbsp;Marta Jędrzejczyk ,&nbsp;Magdalena Mielczarek-Puta ,&nbsp;Gwan Yong Lim ,&nbsp;Małgorzata Podsiad ,&nbsp;Jakub Hoser ,&nbsp;Piotr Bednarczyk ,&nbsp;Marta Struga ,&nbsp;Adam Huczyński","doi":"10.1016/j.ejmcr.2025.100275","DOIUrl":"10.1016/j.ejmcr.2025.100275","url":null,"abstract":"<div><div>Monensin A is a representative of natural ionophores, which exhibit a broad spectrum of biological properties, with the most fascinating being its potent anticancer activity. A very intriguing research direction is the rational chemical modification of the monensin A skeleton to obtain analogs with higher antiproliferative activity and selectivity indices. In this paper, synthetic access to monensin A conjugates with mitochondria-targeting chemical moieties, such as the triphenylphosphonium cation and its analogs, is presented. Furthermore, the obtained derivatives were screened for lead structures with improved anticancer properties and mitochondria-targeting ability. Some of the obtained compounds exhibited greater antiproliferative activity and selectivity than unmodified monensin. Furthermore, biological and biophysical studies have confirmed that the induction of apoptosis by the aforementioned hybrids is linked to targeting of mitochondria in cancer cells. These results prove that such a strategy is a promising approach for the search for new effective drug candidates.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100275"},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134766","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":"Anti-cancer potential of non-curcuminoid bioactive from Curcuma caesia Roxb. (Black Turmeric): Targeting cervical cancer via PI3K/Akt pathway modulation","authors":"Bishnu P. Parida ,&nbsp;Megha Radhakrishnan ,&nbsp;Varsha Goyal ,&nbsp;Astha Sharma ,&nbsp;Rupesh Zarekar ,&nbsp;Mumtaz A. Ansari ,&nbsp;Jasmeet Singh ,&nbsp;Sunita Singh ,&nbsp;Gopeshwar Narayan","doi":"10.1016/j.ejmcr.2025.100273","DOIUrl":"10.1016/j.ejmcr.2025.100273","url":null,"abstract":"<div><div><em>Curcuma caesia</em>, or black turmeric, is a significant medicinal plant used in traditional Indian medicine, including Ayurveda and folk practices. Indigenous communities in the northern Indo-Gangetic plains have utilized it for its analgesic, anti-inflammatory, and anti-infective properties. However, the anti-cancer potential of non-curcuminoid bioactive from <em>Curcuma caesia</em> remains underexplored. The current study investigates the anti-cancer potential of non-curcuminoid bioactive compounds derived from <em>Curcuma caesia</em> rhizome extracts, focusing on their effects against cervical cancer.</div><div>Using high-resolution mass spectrometry (HRMS), key compounds were identified from hexane (HECC) and methanolic (MECC) extracts, among which 3,4-dihydrocoumarin and (+)-ar-turmerone were prominent. <em>In vitro</em> cytotoxicity assays demonstrated that both HECC and MECC selectively inhibited the viability of cervical cancer cell lines, sparing non-tumorigenic HEK293T cells. Mechanistic analyses revealed that 3,4-dihydrocoumarin treatment led to mitochondrial membrane hyperpolarization, suppression of intracellular ROS, and cell cycle arrest at subG1 and G1 phases, while (+)-ar-turmerone had antagonistic modulatory effects. Western blotting confirmed downregulation of PI3K and Akt protein expression. Complementary ADME profiling indicated favorable pharmacokinetic properties, while molecular docking supported strong binding affinity of 3,4-dihydrocoumarin to PI3K and Akt targets, reinforcing its mechanism of action.</div><div><em>Curcuma caesia</em> rhizome fractions, especially 3,4-dihydrocoumarin, exhibit anti-cancer properties by modulating key molecular pathways, including the PI3K/Akt pathway.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088809","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":"M7: A novel in vitro CDK1 inhibitor suppressing colorectal cancer cell proliferation, migration and promoting apoptosis","authors":"Lihong Yang ,&nbsp;Yipan Zhu ,&nbsp;Xinyu Ding ,&nbsp;Jing Sun ,&nbsp;Xinyu Cao ,&nbsp;Zhisong Zhang ,&nbsp;Luyuan Li ,&nbsp;Jianping Lin","doi":"10.1016/j.ejmcr.2025.100271","DOIUrl":"10.1016/j.ejmcr.2025.100271","url":null,"abstract":"<div><h3>Objective</h3><div>Colorectal cancer has a high mortality rate, and drug resistance limits the efficacy of targeted therapies. This study aims to explore the role of M7 in colorectal cancer, identify its targets, and assess its potential as a therapeutic agent.</div></div><div><h3>Methods</h3><div>A multi-stage biochemical screening strategy combined with bio-assay validation was used. In vitro ADP-Glo™ kinase assays verified M7's activity as a potential CDK1 inhibitor.</div></div><div><h3>Results</h3><div>M7 inhibits the proliferation and migration of HCT116 and Lovo cells by down-regulating EMT-related genes, promotes apoptosis by regulating apoptosis-related genes, and targets CDK1, causing G2/M phase arrest.</div></div><div><h3>Conclusions</h3><div>M7, a novel CDK1 inhibitor, shows potential for colorectal cancer drug development.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088810","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":"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}