Bioorganic Chemistry最新文献

{"title":"Recent developments in donepezil-based hybrid molecules as multi-target therapeutics for Alzheimer's disease: A paradigm shift beyond symptomatic treatment.","authors":"Nitin Kumar, Izhar Khan, Jyoti Singh, Krishan Kumar, Virendra Kumar Kushwaha, Smriti Ojha, Sunil Kumar Raman, Gauri Shankar","doi":"10.1016/j.bioorg.2026.110361","DOIUrl":"10.1016/j.bioorg.2026.110361","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder characterized by the gradual loss of cholinergic neurons, leading to cognitive impairment, synaptic dysfunction, and irreversible neuronal degeneration. The multifactorial nature of AD, involving cholinergic deficits, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, neuroinflammation, and metal dyshomeostasis, has limited the clinical success of single-target therapeutic strategies. Although donepezil (DPZ), a clinically approved acetylcholinesterase (AChE) inhibitor, remains one of the most widely prescribed agents for symptomatic management, it does not alter the underlying neurodegenerative processes. Consequently, DPZ has emerged as an attractive medicinal chemistry scaffold for the development of multi-target-directed ligands (MTDLs) that simultaneously modulate multiple interconnected pathological pathways implicated in AD. This review provides a comprehensive and critically organized overview of recent advances in DPZ-based hybrid molecules, emphasizing rational design strategies, hybridization approaches, structure-activity relationships (SAR), molecular mechanisms, and pharmacological profiles. To facilitate a mechanistic understanding, the reported hybrids are systematically classified according to structural modifications of the indanone moiety, the benzylpiperidine moiety, or simultaneous modification of both pharmacophoric regions. Comparative analysis reveals how scaffold engineering, linker optimization, and strategic incorporation of complementary pharmacophores influence cholinesterase inhibition, anti-amyloid activity, antioxidant capacity, neuroprotection, metal chelation, monoamine oxidase inhibition, and blood-brain barrier permeability. Importantly, this review critically examines the current translational landscape, highlighting that despite encouraging in vitro and in vivo findings, no DPZ-based hybrid has yet advanced to clinical evaluation. Key challenges, including pharmacokinetic optimization, metabolic stability, safety, target engagement, and clinical translatability, are discussed together with future medicinal chemistry directions. Rather than presenting DPZ-based hybrids as established disease-modifying therapies, the available evidence supports their role as promising multifunctional lead compounds and valuable molecular platforms for the rational design of next-generation anti-Alzheimer agents. By integrating emerging SAR trends with critical translational perspectives, this review provides a contemporary framework to guide future development of clinically relevant multifunctional therapeutics for AD.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110361"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and biological evaluation of novel 1,3,5-triazine derivatives containing benzo[d]imidazole scaffold as PI3K inhibitors.","authors":"Ju Liu, Nan Li, Runqi Zhang, Xiaozhe Jiang, Yunpeng Zhou, Congjun Xu, Jiaying Ao, Xiaomiao Wang, Chunyan Li, Jiwei Shen, Shi Ding, Ye Chen","doi":"10.1016/j.bioorg.2026.110333","DOIUrl":"10.1016/j.bioorg.2026.110333","url":null,"abstract":"<p><p>Twenty-seven novel 1,3,5-triazine derivatives containing benzo[d]imidazole scaffold were designed, synthesized, and evaluated for anti-tumor activity as PI3Kα inhibitors. Assessment of PI3Kα inhibitory effects revealed that some compounds were highly potent in vitro, with seventeen compounds (LNP1, LNP2, LNP4, LNP7-LNP10, LNP12-LNP18, LNP20, LNP23, and LNP24) showing IC₅₀ values less than 100 nM. Notably, LNP23 and LNP24 showed remarkable potency against PI3Kα with IC₅₀ values of 5.15 nM and 8.88 nM, respectively, and thus they were more potent than positive control drug ZSTK474 (PI3Kα, IC₅₀ = 9.89 nM). Compared with ZSTK474, LNP23 and LNP24 also exhibited increased selectivity for PI3Kα over other class I PI3K isoforms. Evaluation of some compounds on MDA-MB-231, MCF-7, and H1975 cell lines revealed that most of them possessed moderate to outstanding antiproliferative activities. LNP23 demonstrated marked inhibitory activity on cell proliferation, with IC₅₀ values of 6.85 μM (MDA-MB-231), 1.29 μM (MCF-7), and 2.13 μM (H1975). Antitumor mechanism of action of compound LNP23 on MCF-7 cells was investigated, including protein expression of p-PI3K and p-AKT by Western blot assay, AO/EB staining assay, hoechst33342 assay, cell apoptosis assays by flow cytometry, cell cycle analysis by flow cytometry, clone formation assay and transwell migration assay. Additionally, the preliminary SARs of these compounds were also discussed.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110333"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid design reveals a dopamine D3R ligand with promising in vitro ADME properties.","authors":"Hari K Namballa, Michael Dorogan, Sandip Patra, Ashok Gudipally, Li Xie, Lei Xie, Wayne W Harding","doi":"10.1016/j.bioorg.2026.110432","DOIUrl":"10.1016/j.bioorg.2026.110432","url":null,"abstract":"<p><p>There is significant interest in identifying dopamine D3 receptor (D3R) antagonists and partial agonists with favorable drug-like properties as in vivo chemical tools and as experimental therapeutics for substance use disorders. We hypothesized that preserving the classical D3R antagonist pharmacophore while incorporating metabolically favorable structural features into the secondary pharmacophore (\"tail\") region would enable the discovery of selective D3R-targeted ligands with good ADME characteristics. Specifically, orthosteric binding site (\"head\") fragments known to confer D3R affinity were coupled with \"tail\" motifs inspired by non-catechol D1 receptor agonists, which have demonstrated enhanced pharmacokinetic stability. From this work, we have identified a new D3R ligand compound 8o. Compound 8o exhibits high affinity for D3R (2.7 nM) with >30-fold binding preference versus other dopamine receptors. Preliminary functional activity studies suggest that compound 8o is a D3R partial agonist. Docking studies indicate that 8o exhibits D3R interactions that are consistent with a bitopic mode of binding. Compound 8o also shows favorable in vitro ADME properties, that are predictive of good drug-like behavior, making it a promising lead molecule for future D3R in vivo probe and therapeutic optimization.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110432"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoic acid-conjugated chalcones exert antitumor activity via ROS elevation and ferroptosis.","authors":"Xinyue Bi, Haifu Sun, Kaihong Wang, Tianhang Li, Xiang Li, Xiuhua Zhao, Shuang Qiu","doi":"10.1016/j.bioorg.2026.110397","DOIUrl":"10.1016/j.bioorg.2026.110397","url":null,"abstract":"<p><p>Overcoming drug resistance and minimizing off-target toxicity remain major challenges in cancer therapy. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target. Natural chalcones exhibit antitumor properties linked to oxidative stress induction, yet efficacy and selectivity are limited. To achieve this, we designed and synthesized a series of novel α-lipoic acid (LA)-conjugated chalcone derivatives with the aim of disrupting redox and iron homeostasis to induce ferroptosis in cancer cells. Here, we report that these conjugates elevate reactive oxygen species (ROS) levels most prominently in T24 bladder cancer cells, compared to other tested cell lines, leading to potent growth inhibition and suppressed migration. Mechanistically, RNA-seq and functional assays reveal that the lead compound CA-LA triggers ferroptosis by dysregulating cellular iron and glutathione metabolism. Our work presents a rational design strategy for redox-directed antitumor agents and identifies LA-chalcone hybrids as promising candidates for selective bladder cancer therapy via ferroptosis induction.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110397"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Piperlongumine derivatives exert multimodal antitumor effects in prostate cancer via MAPK pathway activation, poly-mechanistic apoptosis induction, and DNMT3A-mediated DNA methylation reduction.","authors":"Yu Zhang, Xue Yang, Xuemei Qiu, Zhurui Li, Danping Chen, Chengpeng Li, Chenchen Li, Yue Zhou, Zhenchao Wang","doi":"10.1016/j.bioorg.2026.110408","DOIUrl":"10.1016/j.bioorg.2026.110408","url":null,"abstract":"<p><p>The high mortality rate of prostate cancer remains a major threat to men's health worldwide, highlighting an urgent need for novel therapeutic agents with improved efficacy and safety profiles. In this study, we employed a rational structural modification strategy to synthesize 14 novel 1,2,3-triazole-hybridized derivatives of piperlongumine (PL), a natural alkaloid with proven anticancer activity. The antiproliferative activity of these derivatives was evaluated in vitro against multiple cancer cell lines (PC-3, A549, T47D, and SMMC-7721), with normal HEK293 cells used to assess their selectivity. All synthesized derivatives (1 M-14 M) exhibited significant antitumor efficacy, with lead compound 11 M showing pronounced inhibition of PC-3 cell proliferation and migration. Mechanistic studies revealed that 11 M induced G2/M phase arrest and triggered mitochondrial-dependent apoptosis, while concurrently activating the ROS-MAPK signaling pathway and autophagic flux. Notably, 11 M attenuated DNMT3A-mediated global DNA hypomethylation. In vivo validation in PC-3 xenograft mice confirmed that 11 M exerted robust tumor growth suppression with low systemic toxicity, accompanied by DNMT3A downregulation and MAPK pathway activation, substantiating its multi-target therapeutic mechanism.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110408"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"10,11-Dehydrocurvularin suppresses non-small cell lung cancer by targeting PAICS and inducing apoptosis.","authors":"Yue Wang, Siyu Chen, Ping Huang, Mewlude Rehmutulla, Yang Xiao, Yaxin Duan, Yang Fu, Xian Xia, Jiangchun Wei, Zhengxi Hu, Qingyi Tong, Yonghui Zhang","doi":"10.1016/j.bioorg.2026.110379","DOIUrl":"10.1016/j.bioorg.2026.110379","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for effective therapeutic agents. Natural products represent an important source of novel anticancer compounds. In this study, we investigated the anti-NSCLC activity of 10,11-dehydrocurvularin (DCV), a fungal-derived macrolide. DCV potently inhibited the proliferation of NSCLC cell lines (A549 and NCI-H1703) in a dose-dependent manner, with IC₅₀ values of 7.92 μM and 5.33 μM, respectively. Furthermore, DCV (30 mg/kg) markedly suppressed tumor growth in A549 xenograft models without causing evident systemic toxicity, as evidenced by reduced tumor volume and weight, with no significant changes in body weight or organ histopathology. Through RNA-seq, drug affinity responsive target stability, and molecular docking analyses, we identified phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a key enzyme in de novo purine biosynthesis, as a direct binding target of DCV. Mechanistically, DCV engagement promoted PAICS protein downregulation and disrupted nucleotide metabolism, leading sequentially to mitochondrial dysfunction, reactive oxygen species accumulation, DNA damage, and cell cycle arrest, ultimately triggering intrinsic apoptosis. Collectively, these findings uncover the anti-NSCLC efficacy and mechanism of DCV, positioning it as a promising natural bioactive lead for subsequent pharmacological development against lung cancer.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110379"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycine-conjugated coumarin-quinazoline hybrids as potent anticancer agents: synthesis, cytotoxicity, SAR and molecular docking studies.","authors":"Nedime Çalışkan, Mustafa Emirik, Fatih Yılmaz, Ozan Emre Eyüpoğlu, Emre Menteşe","doi":"10.1016/j.bioorg.2026.110394","DOIUrl":"10.1016/j.bioorg.2026.110394","url":null,"abstract":"<p><p>A novel series of twelve coumarin-quinazoline hybrids, comprising six glycine-conjugated (9a-f) and six directly linked analogues (8a-f), was synthesized and characterized by FT-IR, ¹H/¹³C NMR, elemental analysis and LC-MS. Cytotoxicity was assessed against PC-3 prostate, PANC-1 pancreatic, A549 lung and MCF-7 breast cancer cell lines by the MTT assay, with HEK-293 cells used to estimate selectivity and with doxorubicin, cisplatin and gemcitabine as reference drugs. Most hybrids were active in the low micromolar range (3.56-6.96 μM) and gave selectivity indices of up to 3.17, compared with 1.14-1.65 for doxorubicin. Compound 9d was the most active against A549 (IC₅₀ = 3.57 ± 0.05 μM), whereas 9c and 9f were the most active against PANC-1 (IC₅₀ = 3.56 ± 0.05 μM), several derivatives exceeding the reference drugs in individual cell lines. Cell-cycle, Annexin V/PI and LDH-release experiments showed a uniform G0/G1 accumulation with depletion of the S-phase population, indicating apoptotic cell death rather than non-specific membrane damage. Molecular docking against PI3Kα, PI3Kγ and ribonucleotide reductase indicated that the glycine linker provides the conformational flexibility required to reproduce key interactions of the co-crystallized ligands, and the G0/G1 arrest was consistent with PI3K rather than RNR inhibition. To the best of our knowledge, glycine conjugation of a coumarin-quinazoline hybrid has not been reported previously, and the results identify it as a substituent- and cell-line-dependent strategy for improving anticancer potency and selectivity.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110394"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"A homologous cell membrane-coated peptide-based USP7 degrader enhances degradation efficiency and anti-tumor activity in gastric Cancer\" [Bioorg. Chem. 180 (2026) 110067].","authors":"Cong-Cong Ma, Cheng-Yun Jin, Nin-Jie Guo, Hong-Min Liu, Qian-Ge Yin, Yu-Bing Wang, Yu-Fei Liu, Yu Zhang, Ning Wang, Guo-Liang Lu, Yan Li, Nan-Zhang, Yi-Chao Zheng","doi":"10.1016/j.bioorg.2026.110308","DOIUrl":"10.1016/j.bioorg.2026.110308","url":null,"abstract":"","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":" ","pages":"110308"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative drug repositioning identifies FDA-approved inhibitors of HSP90AA1 with therapeutic potential in colorectal cancer.","authors":"Xuan Li, Shaofen Xu, Muhammad Waqas, Haoke Zhang, Defang Ouyang, Zunnan Huang","doi":"10.1016/j.bioorg.2026.110262","DOIUrl":"10.1016/j.bioorg.2026.110262","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading cause of cancer mortality, with treatment efficacy limited by tumor heterogeneity and chemotherapy resistance. Drug repositioning can accelerate discovery using FDA-approved agents. Here, we introduce a multi-omics repositioning framework integrating bulk and single-cell data with network pharmacology, structural modeling, and validation and apply it for the first time in CRC. Bulk RNA-seq identified 3480 upregulated and 3816 downregulated genes in TCGA-COADREAD, and 602 upregulated and 744 downregulated in GSE103512. Single-cell RNA-seq revealed 1227 upregulated and 728 downregulated in GSE231559, and 1628 upregulated and 850 downregulated in GSE144735. Integration with cMap and ASGARD yielded 20 candidates; four FDA-approved drugs (rifapentine, danazol, tolbutamide, and triamcinolone) had not been linked to CRC. DepMap PRISM data supported inhibitory activity. Docking and 200 ns molecular dynamics showed stable binding of all four in the HSP90α ATP-binding pocket, with hydrogen bonding and favorable MM/GBSA free energies (-30.59 kcal/mol for danazol to -37.37 kcal/mol for rifapentine; reference NVP-AUY922 -47.99 kcal/mol). Independent triplicate simulations of the reference and top-ranked candidate complexes confirmed the statistical reliability and reproducibility of these structural and energetic descriptors (reference ΔGtotal = -47.90 ± 0.08 kcal/mol). Direct binding of all four compounds to HSP90α was further confirmed by surface plasmon resonance. In vitro, the drugs suppressed proliferation and induced apoptosis in HCT116, LoVo, and HCT-15 cells, with IC₅₀ values of 2.60-13.15 μM. These results identify unreported HSP90AA1 inhibitors in CRC and establish a generalizable repositioning framework.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110262"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and structural characterization of covalent tetrahydroquinoline-based inhibitors of coronavirus 3CLpro.","authors":"Anastasia A Pronina, Dmitriy N Shcherbakov, Artem P Sanchez-Pimentel, Eugeniya V Nikitina, Fedor I Zubkov, Yulia V Meshkova, Mariya K Marenina, Nikolay V Maltsev, Svetlana V Belenkaya, Vadim O Trufanov, Ekaterina A Volosnikova, Anna V Zaykovskay, Sophia S Borisevich, Edward M Khamitov, Dmitriy S Baev, Egor A Mustaev, Alexey Yu Fedorov, Sergey G Arkhipov, Anna V Vlaskina, Anastasia R Nemchinova, Valeriya R Samygina, Oleg V Pyankov, Olga Yarovaya, Wei Xu, Nariman F Salakhutdinov, Mikhail V Khvostov","doi":"10.1016/j.bioorg.2026.110402","DOIUrl":"10.1016/j.bioorg.2026.110402","url":null,"abstract":"<p><p>This study presents the design, synthesis, and evaluation of a novel series of covalent broad-spectrum inhibitors targeting the coronavirus main protease (3CLpro). The designed compounds feature a tetrahydroquinoline (THQ) scaffold functionalized with a chloroacetamide warhead. The most potent of this series in the primary screening assay, 4bf and 5bf, exhibited low micromolar IC₅₀ values against 3CLpro of SARS-CoV-2, SARS-CoV, and MERS-CoV, thereby demonstrating significant cross-reactivity. Structural analysis via X-ray crystallography confirmed covalent binding to the catalytic Cys145 residue. Complementary molecular dynamics simulations revealed stable binding modes and key interactions, highlighting differences in flexibility and residue contacts between the top inhibitors. While in vitro cytotoxicity was observed in Vero E6 cells, acute toxicity studies in mice revealed an LD₅₀ exceeding 1000 mg/kg for the lead compounds, indicating a promising in vivo safety profile. These findings establish substituted tetrahydroquinolines as a viable scaffold for the development of broad-spectrum anticoronaviral agents.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"181 ","pages":"110402"},"PeriodicalIF":5.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862797","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}