Bioorganic & Medicinal Chemistry最新文献

{"title":"Recent developments in synthesis and antimalarial activities of chalcone hybrids","authors":"Ravindar Lekkala ,&nbsp;Revathi Lekkala ,&nbsp;Fei Wen Cheong ,&nbsp;Nurul Izzaty Hassan ,&nbsp;Yee Ling Lau","doi":"10.1016/j.bmc.2025.118512","DOIUrl":"10.1016/j.bmc.2025.118512","url":null,"abstract":"<div><div>Malaria remains a significant cause of mortality globally; development and discovery of novel antimalarial drugs are needed to search for effective antimalarial agents due to resistance against existing drugs. Chalcones, also known as α,β-unsaturated ketones, have been studied due to their varied biological activities, including antimalarial activity. Using hybrid compounds is one helpful strategy to enhance the efficacy of antimalarial drugs and reduce treatment resistance. Hence, the current review intended to introduce various heterocycles like triazole, indole, thiophene, benzimidazole, quinoline, piperidine, pyridine, furan, coumarin, and pyrazole containing chalcone hybrids of promising antimalarial activity reported by the researchers from 2019 to 2025. The structure–activity relationship that has been discussed could provide a useful approach for possible drug design and synthesis based on hybridization between the chalcone core and heterocyclic scaffolds.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118512"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo activity profiles of broad-spectrum bacterial ATP synthase inhibitors","authors":"Suzanne Chamberland ,&nbsp;Audrey Larose ,&nbsp;Guillaume Millette ,&nbsp;Jean-Philippe Langlois ,&nbsp;Julie Côté-Gravel ,&nbsp;Eric Brouillette ,&nbsp;Daniela Droppa Almeida ,&nbsp;Renaud Binette ,&nbsp;Julien A. Delbrouck ,&nbsp;Iryna Diachenko ,&nbsp;Abdelkhalek Ben Jamaa ,&nbsp;Chad Normandin ,&nbsp;Alexandre Murza ,&nbsp;François Malouin ,&nbsp;Pierre-Luc Boudreault","doi":"10.1016/j.bmc.2025.118493","DOIUrl":"10.1016/j.bmc.2025.118493","url":null,"abstract":"<div><div>Tomatidine (<strong>TO</strong>), a natural steroidal alkaloid derived from Solanaceae (<em>e.g.</em>, tomato), is recognized for its narrow-spectrum antibiotic activity, particularly against persistent forms of <em>Staphylococcus aureus</em>, such as small-colony variants (SCVs). Previous studies have shown that <strong>TO</strong> exerts its effect by inhibiting <em>S. aureus</em> ATP synthase. In earlier work, we synthesized nearly 100 <strong>TO</strong> analogs featuring an ethylenediamine linker branched with aromatic substituents at the C3 position, and demonstrated that several of these analogs possess notable antibacterial activity against typical (non-SCV) <em>S. aureus</em> strains, including methicillin-resistant <em>S. aureus</em> (MRSA), with minimum inhibitory concentrations (MICs) ranging from 1 to 4 μg/mL. Among these, analogs incorporating an indole (<strong>TM-247</strong>) or para-substituted aryl moiety (<strong>TM-184</strong>, -I; <strong>TM-218</strong>, -Br; <strong>TM-220</strong>, -Cl; <strong>TM-303</strong>, -CF₃) emerged as lead candidates, exhibiting potent antibacterial activity <em>in vitro</em> against both Gram-positive and Gram-negative bacteria, including <em>S. aureus</em> SCVs. In the present study, we conducted a comprehensive antibacterial profiling of this compound series, including the predecessor compound <strong>TM-02</strong>, against a panel comprising 16 Gram-positive strains, 16 antibiotic-resistant <em>Escherichia coli</em> isolates, and two multidrug-resistant <em>Acinetobacter baumannii</em> strains. <strong>TM-184</strong> emerged as the most promising candidate and was subsequently subjected to an expanded <em>in vitro</em> evaluation across 24 clinically relevant Gram-negative bacterial species. Furthermore, <strong>TM-184</strong> was assessed <em>in vivo</em> using a neutropenic mouse thigh infection model against <em>E. coli</em>, demonstrating significant efficacy and resulting in a substantial reduction in bacterial burden.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118493"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FPhotocleavable PROTACs as tools for dynamic regulation of protein function","authors":"Hanqiao Xu ,&nbsp;Hidetomo Yokoo ,&nbsp;Yosuke Demizu","doi":"10.1016/j.bmc.2025.118491","DOIUrl":"10.1016/j.bmc.2025.118491","url":null,"abstract":"<div><div>Proteolysis-targeting chimeras (PROTACs) have emerged as valuable tools for targeted protein degradation. However, conventional designs generally lack mechanisms for temporal regulation. In this study, we explored photocleavable PROTACs incorporating a nitrobenzyl linker, aiming to achieve light-triggered inactivation of BET protein degradation. Docking simulations indicated that the linker did not disrupt the formation of the ternary complex, and LC–MS/MS analyses indicated that photocleavage occurred rapidly within cells. Cellular experiments demonstrated that the compounds promoted efficient degradation of the BET protein at low concentrations, and recovery assays with UV irradiation indicated that protein expression could be restored after transient depletion. These results suggest that photocleavable PROTACs offer a practical approach to controlling degradation with temporal precision and may provide useful chemical biology tools for investigating the dynamic functions of BET proteins.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118491"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of thiosemicarbazone derivatives as promising SARS-CoV-2 Mpro inhibitors by spectroscopy and microscale thermophoresis","authors":"Xing Xue ,&nbsp;Leyao Chen ,&nbsp;Miao Zhang ,&nbsp;Xiaoyu Chang ,&nbsp;Ruiyong Wang","doi":"10.1016/j.bmc.2025.118501","DOIUrl":"10.1016/j.bmc.2025.118501","url":null,"abstract":"<div><div>Since the outbreak of COVID-19, one key strategy has been to screen inhibitors of the SARS-CoV-2 main protease (Mpro). Mpro is critical for viral replication and a key target for therapeutic development. In this work, we report the design and synthesis of 29 thiosemicarbazone derivatives. Enzymatic inhibition assays showed that 27 compounds exhibited inhibitory activity against Mpro, among which 4 compounds (<strong>1e</strong>, <strong>2c</strong>, <strong>2f</strong>, <strong>3a</strong>) demonstrated significant inhibitory potency, with IC₅₀ values of 5.97 ± 0.98 μM, 4.43 ± 1.67 μM, 10.99 ± 2.39 μM, and 28.88 ± 3.57 μM, respectively. Fluorescence spectroscopy, molecular docking, microscale thermophoresis and molecular dynamics simulations were used to analyze the interaction mechanisms between thiosemicarbazone derivatives and Mpro. Fluorescence results indicated that the fluorescence quenching mechanism of the compounds on Mpro was predominantly static quenching. Hydrogen bonding and hydrophobic interactions were observed in the binding process. Microscale thermophoresis results confirmed that compounds <strong>1e</strong>, <strong>2c</strong> and <strong>2f</strong> exhibit significant binding affinity for Mpro, with K_d values of 4.21 ± 0.35 μM, 3.24 ± 0.28 μM, and 24.26 ± 1.82 μM, respectively. This study provides valuable information for understanding the interaction mechanism between thiosemicarbazone derivatives and Mpro and offers insights into novel Mpro inhibitors.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118501"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of one-bead one-compound cyclic peptide libraries using unpurified proteins from the wheat germ cell-free system to identify protein-protein interaction inhibitors","authors":"Miki Hasegawa ,&nbsp;Akira Nozawa ,&nbsp;Yoshihito Tanaka ,&nbsp;Kohki Kido ,&nbsp;Shinichi Terawaki ,&nbsp;Chikako Takahashi ,&nbsp;Yasumasa Matsumoto ,&nbsp;Yuichi Onda ,&nbsp;Kouhei Tanaka ,&nbsp;Taro Kishimoto ,&nbsp;Hiroshi Sato ,&nbsp;Akihiro Takemiya ,&nbsp;Tatsuya Sawasaki","doi":"10.1016/j.bmc.2025.118492","DOIUrl":"10.1016/j.bmc.2025.118492","url":null,"abstract":"<div><div>Protein-protein interactions (PPIs) are recognized as both attractive and challenging therapeutic targets. Cyclic peptides are particularly well-suited for PPI inhibition due to their ability to effectively interfere with the extensive surface areas involved in these interactions. One-Bead One-Compound (OBOC) libraries have been widely utilized in affinity-based on-bead screening approaches to identify cyclic peptides targeting PPIs. However, a major bottleneck in OBOC library screening is the requirement for purified proteins to ensure screening accuracy. In this study, we present a novel screening platform that integrates an OBOC cyclic peptide library with crude bait proteins produced using a wheat germ cell-free system, eliminating the need for a purification step. This approach facilitates drug discovery for biologically relevant target proteins and those that are difficult to purify. To demonstrate the effectiveness of this method, we selected the p53-murine double minute 2 (MDM2) interaction as a model target and performed a large-scale on-bead binding assay using MDM2. The primary hits identified through this screening exhibited PPI inhibitory activity in the AlphaScreen assay, and docking simulations further verified their binding mode to MDM2. This method offers an efficient strategy for screening cyclic peptides against challenging drug targets, expanding opportunities for PPI-targeted drug discovery.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118492"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Versatile fluorescent homobifunctional crosslinkers: expedient synthesis and application to di-affibody constructs for specific HER2+ cancer cell recognition","authors":"Eric Kaya,&nbsp;Fabienne Fasani,&nbsp;Carlo Pifferi,&nbsp;Catherine Grillon,&nbsp;Vincent Aucagne,&nbsp;Josef Hamacek","doi":"10.1016/j.bmc.2025.118494","DOIUrl":"10.1016/j.bmc.2025.118494","url":null,"abstract":"<div><div>In this contribution we report on the design of new versatile fluorescent linkers (<strong>L1</strong>−<strong>L3</strong>, <strong>L1</strong>^{<strong>N</strong>}) suitable for the covalent assembly of specific recognition motifs to bind biologically relevant targets such as HER2 receptors. The central fluorescent molecular platform emits in red and represents a key building block for the synthesis of conjugates and their subsequent analyses. The presence of amino groups enables straightforward functionalization with bifunctional PEG linkers (NHS, MI) of variable length for further directional bioconjugation. To demonstrate the value of this approach, the linkers were conjugated with chemically synthesized affibodies (AfB, Z_HER2:2891(M9Nle/D37E)), bearing a unique cysteine at N-terminal or C-terminal end. Indeed, this AfB binds the human epidermal growth factor receptor 2 (HER2), which is often overexpressed in different carcinomas, and it is therefore considered as a tumour marker in bioimaging and drug delivery systems. Seven AfB conjugates—three mono-AfBs (<strong>N1</strong>, <strong>N1</strong>^{<strong>N</strong>}, <strong>C1</strong>) and four di-AfBs (<strong>N2</strong>, <strong>N3, C2, C3</strong>)—were obtained through MI-thiol conjugation. The binding of fluorescent mono- and di-affibody (AfB) constructs was evaluated using flow cytometry to demonstrate their ability to interact with the HER2-expressing SKOV3 cells in relation with their structural properties. All tested conjugates specifically bound to HER2 receptors present on SKOV3 cells with nanomolar affinities, and only small differences between constructs were detected. The presence of our fluorescent conjugates bound to the cell surface was visualized using confocal microscopy. In addition, the internalization mechanism of AfB constructs in SKOV3 cells was investigated due to the measurement of their fluorescence following trypsin treatment. In conclusion, our innovative synthetic approach with the integration of a versatile fluorescent platform offers new perspectives for monitoring molecular therapeutics inside cell and for tuning multivalent conjugates for cancer immunotherapy.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118494"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 quinazoline–benzohydrazide and quinazoline–benzothiazole hybrids uncovering a dual EGFR/VEGFR-2 inhibitor with pronounced cytotoxic activity against triple-negative breast Cancer","authors":"Noura F.M. El Hamaky ,&nbsp;Abdelrahman Hamdi ,&nbsp;Waleed A. Bayoumi ,&nbsp;Abdullah A. Elgazar ,&nbsp;Magda N.A. Nasr","doi":"10.1016/j.bmc.2025.118515","DOIUrl":"10.1016/j.bmc.2025.118515","url":null,"abstract":"<div><div>Novel series of quinazoline–benzohydrazide <strong>7a–f</strong> and quinazoline–benzothiazole <strong>10a–f</strong> hybrids were designed and synthesized as potential dual-target inhibitors of EGFR and VEGFR-2. Their anti-proliferative activity was assessed against HeLa, HepG2, MCF-7 and HCT116 cancer cell lines. Among the tested compounds, <strong>7a</strong> demonstrated the most potent activity, with IC₅₀ values ranging from 3.98 to 9.67 μM, comparable with doxorubicin. Most derivatives showed minimal cytotoxicity toward normal WI-38 fibroblasts, indicating a favorable selectivity profile. Notably, compound <strong>7a</strong> exerted significant cytotoxic effect against triple-negative breast cancer (TNBC) MDA-MB-231 cells (IC₅₀ = 7.33 μM), approaching the activity of doxorubicin (IC₅₀ = 2.22 μM). It also markedly inhibited EGFR and VEGFR-2 with IC₅₀ values of 1.67 and 6.72 μM, compared to Erlotinib and Sorafenib, respectively. Flow cytometric analysis revealed that <strong>7a</strong> induced cell cycle arrest at the G0/G1 phase (85.11 %) and promoted apoptosis (29.49 %). Apoptotic profiling further indicated a substantial upregulation of pro-apoptotic Bax (11.73-fold) and downregulation of anti-apoptotic Bcl-2 (0.23-fold), resulting in a striking increase in the Bax/Bcl-2 ratio (51:1). Additionally, <strong>7a</strong> increased the expression levels of caspase-3 and caspase-9 by approximately 7.55- and 5.76-fold, respectively, compared to control/ MDA-MB-231 cells. Molecular docking studies confirmed the strong binding affinity of <strong>7a</strong> within the active sites of both EGFR and VEGFR-2, supporting its proposed mechanism of action. These findings position compound <strong>7a</strong> as a promising lead for further development as a dual EGFR/VEGFR-2-targeting anticancer agent, particularly for aggressive cancers such as TNBC.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118515"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel hybrids of coumarin and quinoline as potential anti-Alzheimer's disease agent","authors":"Shun Li ,&nbsp;Xinrui Li ,&nbsp;Shuanglong Li,&nbsp;Daoyuan Chen,&nbsp;Chunli Xia","doi":"10.1016/j.bmc.2025.118499","DOIUrl":"10.1016/j.bmc.2025.118499","url":null,"abstract":"<div><div>The multifaceted nature of Alzheimer's disease (AD) spurred growing interest in developing multi-target-directed ligands (MTDLs) for its prevention and treatment. Coumarin and quinoline scaffolds, recognized for their broad spectrum of AD-related biological activities including amyloid-β (Aβ) aggregation regulation, cholinesterase (ChE) inhibition, β-secretase 1 (BACE1) inhibition and neuroprotection, were identified as potential building blocks. Here in this study, 24 novel coumarin-quinoline hybrid compounds were rationally designed and synthesized. Inhibition studies targeting Aβ, ChE and BACE1 identified compound <strong>B8</strong> as a promising lead compound. <strong>B8</strong> exhibited effective binding to Aβ, and significantly attenuated Aβ-induced SH-SY5Y cell death by lowering oxidative stress and decreasing cellular apoptosis. Crucially, <strong>B8</strong> demonstrated excellent blood-brain barrier (BBB) permeability, and intragastric administration of <strong>B8</strong> to 7-month-old APP/PS1 transgenic mice resulted in improved cognitive function. This improvement was supported by the protection of hippocampal and cortical neurons from necrosis, attenuation of oxidative stress and inflammation in these brain regions, as well as a reduction in Aβ deposition. These findings highlight the potential of coumarin-quinoline hybrids as a novel class of AD therapeutics, with <strong>B8</strong> emerging as a promising lead candidate warranting further investigation.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118499"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of cationic Pyridinium-Oxazolidinone derivatives as antibacterial agents","authors":"Maxwell Ampomah-Wireko ,&nbsp;Yuequan Wu ,&nbsp;Ye Qu ,&nbsp;Daran Li ,&nbsp;Ruirui Li ,&nbsp;Yuanbo Li ,&nbsp;Hongtao Kong ,&nbsp;Zhi-Hao Li ,&nbsp;Cedric Dzidzor Kodjo Amengor ,&nbsp;Ya-Na Wang ,&nbsp;En Zhang","doi":"10.1016/j.bmc.2025.118502","DOIUrl":"10.1016/j.bmc.2025.118502","url":null,"abstract":"<div><div>Drug-resistant bacteria and biofilm-associated infections remain major challenges in anti-infective therapy, contributing to high morbidity and mortality and emphasizing the need to develop novel antimicrobial agents with a low potential to induce resistance. Toward this, quaternization of compounds has become a viable molecular design approach for developing antibacterial agents. In this study, we report the design, synthesis, and antibacterial evaluation of a series of novel ring-C-modified quaternary ammonium oxazolidinone derivatives bearing various lipophilic substituents (alkyl- and aryl-moieties). The structure-activity relationship (SAR) exploration showed that the introduction of longer alkyl chains had a good effect on the antibacterial activity. Compound <strong>4i</strong> with longest carbon chain exhibited potent antibacterial activity against <em>E. faecalis</em> with a MIC of 4 μg/mL. Furthermore, this pyridinium oxazolidinone not only exhibited a rapid bactericidal effect but also demonstrated a strong activity against <em>E. faecalis</em> biofilms, with no observable tendency for bacteria to develop resistance to <strong>4i</strong> after 20 consecutive passages. Mechanistic studies revealed that <strong>4i</strong> disrupted glutathione (GSH)/reactive oxygen species (ROS) homeostasis, thereby inducing lethal oxidative stress, leading to ROS accumulation and bacterial death. Compound <strong>4i</strong> also showed low toxicity toward mammalian cells. Overall, our results suggest that incorporating quaternary ammonium salts into oxazolidinones will provide promising strategy for designing novel oxazolidinone derivatives with potent antimicrobial activity and low toxicity against mammalian cells.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118502"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the power of quinazoline derivatives: a new frontier in targeted cancer therapy","authors":"Hao-Zhe Long ,&nbsp;Meng-Jie Fu ,&nbsp;Xin-Qian Ji ,&nbsp;Cong-Jun Liu ,&nbsp;Bo Wang ,&nbsp;Ya Gao ,&nbsp;Hui-Min Liu ,&nbsp;Yi-Chao Zheng ,&nbsp;Hong-Min Liu ,&nbsp;Xing-Jie Dai","doi":"10.1016/j.bmc.2025.118497","DOIUrl":"10.1016/j.bmc.2025.118497","url":null,"abstract":"<div><div>Quinazoline-based scaffolds represent a class of nitrogen-containing heterocycles distinguished by their structural versatility and broad-spectrum anticancer activities, positioning them as key elements in targeted cancer therapy. This review highlights the role of quinazoline derivatives as potent small-molecule inhibitors targeting diverse oncogenic drivers. They effectively modulate critical receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and cellular-mesenchymal epithelial transition factor (c-Met); non-receptor serine/threonine kinases including cyclin-dependent kinases (CDKs), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Aurora kinases, and hematopoietic progenitor kinase 1 (HPK1); as well as epigenetic, cytoskeletal, and DNA-interacting proteins. Recent advances in structure-activity relationship (SAR) studies, binding analyses, and preclinical evaluations have facilitated scaffold optimization to counter resistance mutations and improve pharmacokinetic properties. Collectively, clinical and experimental evidence underscores quinazoline derivatives as a robust platform for developing next-generation targeted anticancer agents.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118497"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}