Medicinal Chemistry Research最新文献

{"title":"Advances in preclinical studies of ginsenoside Rh2 in antitumor therapy","authors":"Zheng Xu,&nbsp;Guanghuan Shen,&nbsp;Zhihua Xing,&nbsp;Jianghan Luo,&nbsp;Yu Zhu,&nbsp;Xuan Liu,&nbsp;ShiHao Li,&nbsp;Hao Wang,&nbsp;Linlin Cui","doi":"10.1007/s00044-025-03462-w","DOIUrl":"10.1007/s00044-025-03462-w","url":null,"abstract":"<div><p>Cancer is a wound that never heals and is the second leading cause of death worldwide. Ginsenoside Rh2 (G-Rh2) is the main active substance extracted from Panax ginseng c.a. Meyer, has anticancer activity. G-Rh2 can inhibit tumor cell proliferation, migration, invasion, and neovascularization, regulate immune function, and induce apoptosis and cycle blockade in vitro and in vivo. In addition, G-Rh2 can be used as an adjuvant to chemotherapeutic drugs to enhance their anticancer effects and reverse adverse effects. In this study, the anti-tumor mechanism of G-Rh2 was organized and reviewed by reviewing relevant reports in recent years to provide guidance for the application of G-Rh2 in clinical tumor therapy.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 10","pages":"2075 - 2085"},"PeriodicalIF":3.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro cytotoxicity evaluation of triphenylphosphonium (TPP) conjugates of some acetylenated nucleic bases and their analogues","authors":"Olga V. Andreeva,&nbsp;Alexandra D. Voloshina,&nbsp;Anna P. Lyubina,&nbsp;Andrey A. Parfenov,&nbsp;Bulat F. Garifullin,&nbsp;Irina Yu. Strobykina,&nbsp;Mayya G. Belenok,&nbsp;Olga B. Babaeva,&nbsp;Vasily M. Babaev,&nbsp;Liliya F. Saifina,&nbsp;Vyacheslav E. Semenov,&nbsp;Vladimir E. Kataev","doi":"10.1007/s00044-025-03459-5","DOIUrl":"10.1007/s00044-025-03459-5","url":null,"abstract":"<div><p>In this work, we designed and synthesized 12 triphenylphosphonium (TPP) conjugates of acetylenated nucleic bases (uracil, thymine) and their analogues (6-methyluracil, quinazoline-2,4-dione) and evaluated their in vitro cytotoxicity against 9 human cancer cell lines M-HeLa, HuTu 80, MCF-7, T 98 G, A 549, DU-145, SK-OV-3, PC-3, A-375 and two lines of normal human cells RPMI 1788 and WI-38. All synthesized TPP-conjugates showed high cytotoxicity (IC₅₀ values in the range of 0.1–7.3 µM) against all used human cancer cell lines. The mechanisms of cytotoxic action were studied for the lead compounds <b>2c</b>,<b>d</b>, <b>4c</b>,<b>d</b> which exhibited very high cytotoxicity (IC₅₀ = 0.2–0.3 μM) against PC-3 cancer cells. The flow cytometry method using Annexin V and propidium iodide (PI) has shown that the lead compounds cause apoptosis of PC-3 cells. With the help of flow cytometry using cationic carbocyanine dye JC-1, it was found that the lead compounds cause a significant dose-dependent decrease in the mitochondrial membrane potential of PC-3 cancer cells, that induces apoptosis along the mitochondrial pathway. Significant ROS production in PC-3 cells after their treatment with the lead compounds <b>2c</b>,<b>d</b> was detected by flow cytometry using CellROX® Deep Red fluorogenic probe. Enzyme-linked immunosorbent assay (ELISA) found that the lead compounds activated apoptosis-initiating caspase-9 and blocked anti-apoptotic Bcl-2 protein in PC-3 cancer cells. This experimental fact was explained by molecular docking.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1958 - 1973"},"PeriodicalIF":3.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wedelia species: phytochemistry, pharmacology, toxicology, nanoformulation, and synthetic modification- an extensive review","authors":"Ta Thi Thu Thuy,&nbsp;Do Thi Lan Huong,&nbsp;Duong Quang Huan,&nbsp;Nguyen Thi Hanh,&nbsp;Huynh Thi Ngoc Ni,&nbsp;Phan Hong Minh,&nbsp;Ninh The Son","doi":"10.1007/s00044-025-03452-y","DOIUrl":"10.1007/s00044-025-03452-y","url":null,"abstract":"<div><p><i>Wedelia</i> species (the Asteraceae family) are renowned for treating several inflammation-related diseases clinically, such as pertussis and pharyngitis. Plants of the genus contain diverse bioactive metabolites. The review comprehensively describes scientific investigations regarding <i>Wedelia</i> species, comprising phytochemical record, pharmacological value, toxicological evaluation, and nano- and semisynthetic preparations. Four online sources Web of Science, Scopus, Google Scholar, and PubMed have been extensively used in the search for English references. The phytochemical profile of <i>Wedelia</i> species consisted of 290 secondary metabolites, which can be classified as terpenoids, phytosterols, saponins, phenolics, and others. Sesquiterpenoids and <i>ent</i>-kaurane diterpenoids were the major compounds. <i>Wedelia</i> species are also rich in terpenic essential oils. <i>Wedelia</i> constituents have a broad panel of pharmacological activities, such as anticancer, anti-inflammatory, antioxidant, antimicrobial, antidiabetic, antinociceptive, and antiviral activities. It is also useful in applications that protect the neurons, liver, and bones, and aid in wound healing. Bezofuran, wedelolactone, and two major diterpenoids, kaurenoic acid and grandiflorenic acid, are likely the bioactive molecules. Various molecular mechanisms of anti-inflammatory action have been proposed, including the nuclear factor kappa B/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathway. <i>Wedelia</i> extracts were associated with an LD₅₀ value of more than 2000 mg/kg to rats. Nanoformulation and semisynthesis would enhance the pharmacological activities of <i>Wedelia</i>. In vitro and in vivo pharmacological studies for a vast number of <i>Wedelia</i> isolates are encouraged. Developing new formulations with more therapeutic value is expected.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1855 - 1887"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent α-glucosidase inhibitory activity of inoscavin A from fruiting bodies of Fulvifomes fastuosus: Mechanism of action, molecular docking and ADMET","authors":"Khemika Singmahan,&nbsp;Chiraphat Takpho,&nbsp;Nadtanet Nunthaboot,&nbsp;Worrawat Promden,&nbsp;Ruchilak Rattarom,&nbsp;Khwanyuruan Naksuwankul,&nbsp;Kusavadee Sangdee,&nbsp;Aphidech Sangdee,&nbsp;Masahiko Isaka,&nbsp;Prapairat Seephonkai","doi":"10.1007/s00044-025-03461-x","DOIUrl":"10.1007/s00044-025-03461-x","url":null,"abstract":"<div><p>The DPPH radical scavenging, <i>α</i>-glucosidase inhibitory, nitric oxide (NO) inhibitory, and cytotoxic activities of the extracts from fruiting bodies of wood-rot basidiomycete <i>Fulvifomes fastuosus</i> were evaluated in this study. While the CH₂Cl₂ extract was biologically inactive, chromatographic fractionation led to the isolation of two chlorinated hydroquinone derivatives, drosophilin A methyl ether (DAME; <b>1</b>) and drosophilin A (DA; <b>2</b>). The EtOAc-partitioned fraction, obtained from the partitioning of the MeOH extract, exhibited strong <i>α</i>-glucosidase and NO inhibitory activities. Further investigation led to the isolation of inoscavin A (<b>3</b>) as the major constituent, along with inoscavin E (<b>4</b>) and polyphenols (<b>5</b>–<b>7</b>). Inoscavin A demonstrated potent <i>α</i>-glucosidase inhibition (IC₅₀ = 3.22 µM), surpassing acarbose by 59-fold, and exhibited non-competitive inhibition kinetics (<i>K</i>ᵢ = 3.25 µM). Molecular docking studies supported an allosteric binding mode. It also displayed favorable drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles, including good solubility, high intestinal absorption, low central nervous system (CNS) penetration, and absence of hepatotoxicity. These results suggest that <i>F. fastuosus</i> is a promising source of antidiabetic agents, with inoscavin A as a principle active compound.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1989 - 2001"},"PeriodicalIF":3.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization and biological evaluation of formononetin derivatives as anticancer agents","authors":"Neha Bhardwaj,&nbsp;Kajal Kaliya,&nbsp;Sudesh Kumar Yadav,&nbsp;Ankit Saneja","doi":"10.1007/s00044-025-03460-y","DOIUrl":"10.1007/s00044-025-03460-y","url":null,"abstract":"<div><p>Formononetin (FMN), a natural isoflavone with broad biological activity, has emerged as a potential lead molecule as an anticancer agent. In this work, different FMN ester derivatives were synthesized via an acylation reaction (3a-d). The structural characterization and purity of the compounds were confirmed through NMR, HRMS, and HPLC analysis. Among the synthesized derivatives, the 4-Morpholinecarbonyl chloride conjugated FMN (FMN-4Morpho; 3b) demonstrated significantly (p &lt; 0.05) enhanced cytotoxicity against multiple cancer cell lines, including A549, B16F10, and 4T1, while showing no notable toxicity up to 200 μM in non-cancerous L929 fibroblasts and RAW 264.7 macrophages, indicating good biocompatibility. The mechanistic evaluations in A549 and 4T1 cells revealed elevated ROS production, disruption of mitochondrial membrane potential, and increased apoptosis, as revealed by JC-1 and Annexin V-FITC/PI staining. Additionally, FMN-4Morpho suppressed colony formation and cell migration, downregulated cyclin A, cyclin D1, MMP-2, and MMP-9, and upregulated p53 and Bax expression, thereby lowering the Bcl-2/Bax ratio. The findings highlight FMN-4Morpho as a promising therapeutic candidate with improved anticancer efficacy.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1974 - 1988"},"PeriodicalIF":3.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effects of iridoid glycosides: a comprehensive review of mechanisms of action and structure-activity relationships","authors":"Xinyue Zheng,&nbsp;Wenwen Li,&nbsp;Mingtao Wang,&nbsp;Haiyi Gao,&nbsp;Yian Zhao,&nbsp;Peiliang Dong,&nbsp;Hua Han","doi":"10.1007/s00044-025-03456-8","DOIUrl":"10.1007/s00044-025-03456-8","url":null,"abstract":"<div><p>Inflammation plays a crucial role in the onset and progression of various diseases. However, current anti-inflammatory therapies often produce adverse effects that limit their clinical utility. This review focuses on the therapeutic potential of iridoid glycosides, a class of monoterpenoid compounds known for their anti-inflammatory properties. Drawing on literature from PubMed and Google Scholar, this study comprehensively examines eight well-studied iridoid glycosides in terms of their sources, administration methods, dosages, target inflammatory models, and mechanisms of action. The compounds were found to modulate critical signaling pathways, including NF-κB, NLRP3 inflammasome, MAPK, and JAK-STAT, thereby suppressing key inflammatory cytokines such as TNF-α, IL-1β, and IL-6, while also activating antioxidant defenses. Structure–activity relationship analysis suggests that glycosyl, ester, and epoxy groups are essential pharmacophores for their bioactivity. Collectively, these findings underscore the promise of iridoid glycosides as effective and safer alternatives for managing inflammatory diseases.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1833 - 1854"},"PeriodicalIF":3.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and evaluation of potent AAK1 inhibitors through structure-based pharmacophores, virtual screening and bioassay screening","authors":"Mahmoud A. Al-Sha’er,&nbsp;Afnan A. Alzaghari,&nbsp;Mutasem O. Taha","doi":"10.1007/s00044-025-03455-9","DOIUrl":"10.1007/s00044-025-03455-9","url":null,"abstract":"<div><p>This study employed structure-based drug design to discover novel inhibitors of Adaptor Associated Kinase 1 (AAK1) as potential anticancer agents. A total of 300 pharmacophore models were generated from AAK1 co-crystallized protein structures, from which the optimal model (<b>Hypo1</b>) was selected based on receiver operating characteristic (ROC) analysis (AUC = 82.3%) and further refined using shape-based alignment. Virtual screening of the National Cancer Institute (NCI) database yielded 7399 initial hits, which were narrowed down to 3481 compounds through Lipinski’s rule of five and SMARTS pattern filtering. Subsequent molecular docking against the AAK1 active site identified 438 candidates, of which the top 40 were selected for biological evaluation. Among these, Hit 5 (NCI 157865) exhibited the most potent AAK1 inhibition (IC₅₀ = 1.03 µM), with other active hits showing IC₅₀ values ranging from 1.87 to 7.49 µM. MTT assays confirmed the anticancer activity of Compound 5, with IC₅₀ values of 11.46 µM against MCF7 and 69.37 µM against A549 cell lines. The compound’s potency is attributed to key hydrophobic interactions and hydrogen bond acceptor features. These results highlight Compound 5 as a promising lead candidate for further development as an anticancer agent.</p><div><figure><div><div><picture><source><img></source></picture></div><div><p><b>Hypo1</b> fitted against hit <b>5</b> as compared to its 2D interactions within AAK1 binding site with IC₅₀ = 1.05 μM</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1945 - 1957"},"PeriodicalIF":3.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in saponin-based vaccine adjuvants","authors":"Linggai Cao,&nbsp;Ping Dong,&nbsp;Jie Liu,&nbsp;Jie Zhang,&nbsp;He Xie,&nbsp;Shizhou Yu,&nbsp;Jianfeng Zhang","doi":"10.1007/s00044-025-03453-x","DOIUrl":"10.1007/s00044-025-03453-x","url":null,"abstract":"<div><p>Saponin-based adjuvants have emerged as promising candidates for enhancing vaccine efficacy by modulating immune responses. Derived primarily from plant and marine sources, saponins possess unique amphiphilic structures that contribute to their potent immunostimulatory properties. This review explores the advancements in saponin-based vaccine adjuvants, focusing on their immunomodulatory mechanisms, structural diversity, and applications. QS-21, a triterpenoid saponin from <i>Quillaja saponaria</i>, is the most extensively studied and has been incorporated into licensed vaccines such as Shingrix, Mosquirix, and Arexvy. However, the limitations of natural saponin-derived adjuvants, including hemolytic toxicity, hydrolytic instability, and low yield, have driven research toward semi-synthetic and synthetic analogs. Advances in synthetic biology and biosynthetic pathway elucidation have enabled the development of next-generation saponin-based adjuvants with enhanced potency and reduced toxicity. This review provides a comprehensive overview of the current state of saponin-based adjuvant research, highlighting their potential to revolutionize vaccine formulations and contribute to global public health initiatives.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1817 - 1832"},"PeriodicalIF":3.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03453-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidiabetic evaluation of novel thienopyrimidinone-thiazolidinedione hybrids complemented with kinetic and computational investigations","authors":"Pule Seboletswe,&nbsp;Gobind Kumar,&nbsp;Nontobeko Gcabashe,&nbsp;Sanjeev Dhawan,&nbsp;Neha Manhas,&nbsp;Lungisani Khubone,&nbsp;ALmahi Idris,&nbsp;Md. Shahidul Islam,&nbsp;Parvesh Singh","doi":"10.1007/s00044-025-03449-7","DOIUrl":"10.1007/s00044-025-03449-7","url":null,"abstract":"<div><p>Diabetes mellitus (DM) is a complex disease, and its treatment/management frequently requires the use of different drugs with distinct modes of action. Unfortunately, many of the current medications come with an increasing plethora of adverse effects. Consequently, DM poses a significant challenge to the global health system. Carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase have emerged as well-known therapeutic targets for the regulation of postprandial glucose levels. Herein, we report the design and synthesis of 20 novel molecular hybrids encompassing thienopyrimidinone and thiazolidinedione pharmacophores that can inhibit α-amylase and α-glucosidase and prevent oxidative stress. Several derivatives showed more potency than the standard drug acarbose. Compound <b>12q</b> (IC₅₀ = 38.89 ± 0.50 µM) with alkyl chain length <i>n</i> = 4 exhibited four-fold superior potency to acarbose (IC₅₀ = 174.40 ± 2.63 µM) against α-amylase, while compound <b>12t</b> (IC₅₀ = 41.94 ± 4.76 µM) also with alkyl chain length <i>n</i> = 4 exhibited seven-fold higher activity than acarbose (IC₅₀ = 282.80 ± 1.46 µM) against α-glucosidase. Enzyme kinetic studies further revealed these compounds (<b>12q</b> and <b>12t</b>) to be mixed inhibitors of the respective enzymes and were extensively engaged in interactions with their targets based on molecular docking simulations.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1929 - 1944"},"PeriodicalIF":3.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03449-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and biological evaluation of coumarin derivatives as anti-lung adenocarcinoma agents via induction of apoptosis and autophagy: in vitro and in vivo studies","authors":"Shi Yin,&nbsp;Pengyu Zhao,&nbsp;Qi Liao,&nbsp;Debin Chen,&nbsp;Chenjuan Zeng,&nbsp;Yuefei Geng,&nbsp;Funeng Geng","doi":"10.1007/s00044-025-03451-z","DOIUrl":"10.1007/s00044-025-03451-z","url":null,"abstract":"<div><p>Lung cancer represents a significant public health challenge, with non-small cell lung cancer (NSCLC) being the predominant subtype, underscoring the urgent need for improved therapeutic strategies. The limited efficacy of conventional chemotherapy has catalyzed the exploration of alternative treatment modalities. Natural products play a pivotal role in drug discovery, with structural modifications being integral to pharmaceutical research. This study presents novel coumarin derivatives that exhibit potential as candidate molecules for the treatment of lung adenocarcinoma. Among the synthesized compounds, compound <b>4f</b> demonstrated potent inhibitory effects on PC9 cells, with an IC₅₀ value of 4.08 μM. In vitro analyses demonstrated that <b>4f</b> significantly inhibited the proliferation and migration of PC9 cells by downregulating the expression of mTOR, which subsequently induced autophagic cell death. In vivo studies indicated that <b>4f</b> effectively targets mTOR, leading to the suppression of tumor growth while exhibiting a favorable safety profile. These findings support the advancement of new coumarin derivatives as promising therapeutic agents for lung adenocarcinoma.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1914 - 1928"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}