Bioorganic & Medicinal Chemistry最新文献

{"title":"Synthesis and multitarget inhibitory effect of indole-based ethyl cinnamate derivatives against SARS-CoV-2 Mpro and cathepsins for broad-spectrum anti-coronavirus activity","authors":"Andrea Citarella ,&nbsp;Giulia Sibille ,&nbsp;Davide Moi ,&nbsp;Alessandro Dimasi ,&nbsp;Tommaso Braga ,&nbsp;Lorenzo Dal Col ,&nbsp;Lorenzo Ruberto ,&nbsp;Stefano Pieraccini ,&nbsp;Maurizio Sironi ,&nbsp;Nicola Micale ,&nbsp;Tanja Schirmeister ,&nbsp;Valerio Fasano ,&nbsp;Alessandra Silvani ,&nbsp;Clelia Giannini ,&nbsp;Giorgio Gribaudo ,&nbsp;Daniele Passarella","doi":"10.1016/j.bmc.2025.118258","DOIUrl":"10.1016/j.bmc.2025.118258","url":null,"abstract":"<div><div>The experience of the SARS-CoV-2 pandemic has highlighted the urgent need to develop broad-spectrum antivirals (BSA) agents capable of targeting viral and/or host factors essential for infection as undeniable weapons against future coronavirus threats with potential pandemic perspectives. In this study, we report the synthesis and biological evaluation of a novel series of indole-based ethyl cinnamate derivatives designed as multitarget inhibitors of both SARS-CoV-2 Main Protease (M^pro) and human cathepsin, namely CatL and CatS, key enzymes involved in viral replication and entry. Enzymatic assays showed that several compounds exert significant inhibition on multiple targets. Structure-activity relationship (SAR) studies highlighted the critical role of the <em>tert</em>-leucine (Tle) residue at <em>P</em>2 position of these (pseudo)dipeptides, which proved to be essential for multitarged enzyme inhibition and antiviral activity. In antiviral assays against representative α- (hCoV-229E) and β-coronavirus (hCoV-OC43), <strong>12</strong> (EC₅₀ = 4.09 µM for hCoV-OC43, 0.77 µM for hCoV-229E), <strong>20</strong> (EC₅₀ = 6.68 µM for hCoV-OC43, 0.62 µM for hCoV-229E), and <strong>3</strong> (EC₅₀ = 2.96 µM for hCoV-OC43, 0.64 µM for hCoV-229E) restricted viral replication with high selectivity values (SI = 98, 56, and 101, respectively). Time-of-drug-addition experiments then revealed that <strong>12</strong> primarily inhibited viral entry by targeting CatL, whereas <strong>20</strong> affected both entry and post-entry stages of hCoV replication cycle likely thanks to its dual-inhibitory activity against both CatL and M^pro. These findings support the development of multitarget inhibitors as promising antivirals able to inhibit both α- and β-coronavirus, so as to reduce the risk of resistance associated with single-target agents. Furthermore, the demonstrated effectiveness of Tle-containing indole-based cinnamates as BSA highlights their potential in the context of the strategic framework for pandemic preparedness.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118258"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137784","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":"Innovative synthesis and purification method of fluorescent and bifunctional substrates for self-labelling protein tags","authors":"Anna Sategna ,&nbsp;Matteo Leoncini ,&nbsp;Diego Caprioglio ,&nbsp;Rosanna Mattossovich ,&nbsp;Riccardo Miggiano ,&nbsp;Alberto Minassi ,&nbsp;Rosa Merlo","doi":"10.1016/j.bmc.2025.118260","DOIUrl":"10.1016/j.bmc.2025.118260","url":null,"abstract":"<div><div>Self-labelling protein tags, including SNAP-tag, HaloTag, and CLIP-tag, have revolutionized molecular biology by enabling precise visualization and manipulation of proteins within living cells. These systems use suicidal proteins that react with synthetic substrates to facilitate the attachment of fluorescent dyes, which offer advantages such as flexibility in dye selection and compatibility with advanced imaging techniques like fluorescence microscopy and fluorimetry. This paper presents a new methodology for the synthesis and high-yield purification of fluorescent probes for SNAP-tag, CLIP-tag, and HaloTag, while also investigating their kinetic parameters. A key innovation is the design of a bifunctional molecule capable of selectively cross-linking SNAP-tag and HaloTag proteins, overcoming potential cross-reactivity between SNAP-tag and CLIP-tag. The synthesis was achieved with improved reaction yields using flash chromatography, replacing traditional HPLC methods, and characterized using NMR spectroscopy and mass spectrometry. Biochemical assays demonstrated the suitability of the new substrates for various AGTs and HaloTag, with kinetic studies revealing their efficacy at different temperatures. Additionally, the bifunctional linker was shown to enable the simultaneous capture of SNAP-tag and HaloTag proteins, with fluorescence assays and native gel electrophoresis confirming the formation of protein complexes. These advancements in substrate production, characterization, and cross-linking design enhance the versatility of SLPs, offering new opportunities for studying protein dynamics and interactions in live cells. This work paves the way for further biotechnological applications of these powerful tools.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118260"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137783","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 medicinal diversity of benzoic acid containing molecules: Insights on druggable targets for type 2 diabetes mellitus","authors":"Kajal Rani ,&nbsp;Preety Kumari ,&nbsp;Anita Kumari ,&nbsp;Debarshi Mondal ,&nbsp;Priya Bisht ,&nbsp;Rupali Kohal ,&nbsp;Vivek Asati ,&nbsp;Ghanshyam Das Gupta ,&nbsp;Sant Kumar Verma","doi":"10.1016/j.bmc.2025.118245","DOIUrl":"10.1016/j.bmc.2025.118245","url":null,"abstract":"<div><div>Benzoic acid, a versatile aromatic carboxylic acid, has gained attention as a promising scaffold for developing therapeutic agents targeting diabetes mellitus, a chronic metabolic disorder characterized by persistent hyperglycemia and associated complications. Structural analysis elucidated how modifications to the benzoic acid structure enhance pharmacological efficacy by influencing glucose metabolism, insulin sensitivity, and oxidative stress pathways. Notably, benzoic acid derivatives exhibit inhibitory effects on key enzymes such as protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase-4 (DPP-4), α-glucosidase, peroxisome proliferator-activated receptor gamma (PPAR-γ), and aldose reductase, which are implicated in diabetes pathophysiology. Molecular docking simulations further reveal the molecular interactions underlying these effects, supporting the potential of these derivatives in multi-targeted therapies. This review integrates findings from SAR studies of benzoic acid synthesized over two decades, showcasing significant advancements in the design and development of benzoic acid derivatives as promising candidates for the effective management of diabetes and its associated complications.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118245"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147928","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 and synthesis of Sorafenib analogues and evaluation of their ferroptosis-inducing effects in tumor cells","authors":"Changxu Ning ,&nbsp;Jiani Tan ,&nbsp;Rui Cai ,&nbsp;Zhongxiang Zhou ,&nbsp;Jiangye Zhang ,&nbsp;Yiming Yao ,&nbsp;Xiaomin Liu ,&nbsp;Shisheng Wang ,&nbsp;Yueqing Li ,&nbsp;Yijiang He ,&nbsp;Xiuhan Guo","doi":"10.1016/j.bmc.2025.118255","DOIUrl":"10.1016/j.bmc.2025.118255","url":null,"abstract":"<div><div>Ferroptosis, a newly discovered form of cell death, has garnered significant attention in recent years, particularly in the development of anticancer drugs. This study was based on the marketed anticancer drug sorafenib and involved the design and synthesis of 12 novel derivatives of pyrrolo[2,1-f][1,2,4]triazine and quinazoline with various linkers to explore their potential to induce ferroptosis in cancer cells. Activity evaluations in three different cancer cell lines (HepG2, MDA-MB-231, and HT-1080) revealed that compounds using squaramide as a linker, particularly <strong>N-2-c1</strong>, exhibited significant anti-proliferative effects against ferroptosis-sensitive HT1080 cells, outperforming Sorafenib. Further mechanistic studies demonstrated that <strong>N-2-c1</strong> effectively induced ferroptosis in HT1080 cells, leading to increased intracellular reactive oxygen species (ROS), lipid peroxidation accumulation, membrane potential damage, and elevated LDH release. Atomic force microscopy was employed to observe morphological changes in the cells, confirming ferroptosis-like alterations in HT1080 cells treated with <strong>N-2-c1</strong>. Additionally, computational docking analyses indicated that <strong>N-2-c1</strong> exhibited superior binding affinity to GPX4 compared to Sorafenib and the control compound <strong>7j-a1</strong>, further supporting its potential as a ferroptosis inducer. In conclusion, the compound <strong>N-2-c1</strong> demonstrated selective induction of ferroptosis in tumor cells, providing a novel approach for the development of new anticancer therapies. Further investigations were recommended to elucidate the mechanisms and assess the clinical applicability.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118255"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147929","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":"Recent breakthroughs in synthetic small molecules targeting SARS-CoV-2 Mpro from 2022 to 2024","authors":"Laura Braconi ,&nbsp;Alice Sosic ,&nbsp;Letizia Crocetti","doi":"10.1016/j.bmc.2025.118247","DOIUrl":"10.1016/j.bmc.2025.118247","url":null,"abstract":"<div><div>Among the identified targets for developing anti-coronavirus therapies, SARS-CoV-2 M^pro stands out as one of the most promising due to its crucial role in viral replication and its low mutability across various coronaviruses, making it a potential broad-spectrum target. Currently, although the approved drugs targeting M^pro are peptidomimetic inhibitors with an adequate efficacy, they exhibit relatively poor pharmacokinetic properties commonly associated with peptide-based compounds. On the contrary, using non-peptidic small-molecules M^pro inhibitors can offer many advantages, including reduced off-target toxicity, improved metabolic stability and drug-like properties more appropriate for oral administration. This topic has sparked interest in the scientific community, leading to the publication of numerous studies in recent years. In this review, we summarize the most recent progress over the past two years in the identification and development of synthetic small-molecule inhibitors of SARS-CoV-2 M^pro.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118247"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123536","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":"Drug discovery targeting protein arginine methyltransferase 5 (PRMT5): an update","authors":"Zhouyang Gu ,&nbsp;Weizheng Kong ,&nbsp;Xing Liu ,&nbsp;Liangju Hu ,&nbsp;Yucheng Zhou ,&nbsp;Zhenchu Liang ,&nbsp;Minyue Zhang ,&nbsp;Dongyin Chen ,&nbsp;Fei Li ,&nbsp;Weilin Chen","doi":"10.1016/j.bmc.2025.118240","DOIUrl":"10.1016/j.bmc.2025.118240","url":null,"abstract":"<div><div>Protein arginine methyltransferase 5 (PRMT5) plays an important role in regulating gene expression, cell differentiation and development, and chromatin structure by catalyzing the methylation of histones and non-histone proteins. The aberrant expression of PRMT5 is closely associated with the occurrence and progression of various diseases, particularly malignant tumors. Accordingly, developing potent and specific PRMT5 inhibitors may provide a potential novel therapeutic approach. In this Perspective, we highlight the structures, the biological functions, regulatory mechanisms, relevant signaling pathways, and associations with cancer development of PRMT5, as well as the recent advances in drug discovery strategies targeting PRMT5. The challenges, opportunities, and future directions for developing PRMT5 inhibitors and degraders are also discussed.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118240"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115758","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":"Advances in MLKL-targeted inhibitors and PROTACs for necroptosis therapeutics","authors":"Pengcheng Dai ,&nbsp;Yufeng Xin ,&nbsp;Xiuting Qin ,&nbsp;Hao Ma ,&nbsp;Chunlin Zhuang","doi":"10.1016/j.bmc.2025.118246","DOIUrl":"10.1016/j.bmc.2025.118246","url":null,"abstract":"<div><div>Necroptosis is a highly regulated form of cell death. Mixed lineage kinase domain-like protein (MLKL) serves as its central effector and plays a critical role in various physiological and pathological processes. Given its close association with multiple diseases, MLKL has emerged as a promising therapeutic target. This review highlights recent advances in the development of necroptosis inhibitors and degraders targeting MLKL. The optimization of active compounds, structural modifications, and the applications of proteolysis-targeting chimeras (PROTACs) are emphasized. Furthermore, this study systematically evaluates the structural characteristics and biological activities of these compounds, thereby providing critical insights to inform future investigations and pharmaceutical development within this field.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118246"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115757","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":"Oxidative complexity: The role of ROS in the tumor environment and therapeutic implications","authors":"Tingfeng Shen ,&nbsp;Yutong Wang ,&nbsp;Linmao Cheng ,&nbsp;Ann M. Bode ,&nbsp;Ya Gao ,&nbsp;Shuntong Zhang ,&nbsp;Xue Chen ,&nbsp;Xiangjian Luo","doi":"10.1016/j.bmc.2025.118241","DOIUrl":"10.1016/j.bmc.2025.118241","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) constitutes a group of reactive molecules that play a critical role in biological processes. Varying ROS levels have been frequently observed in cancer cells and the tumor microenvironment (TME). The role of ROS displays significant complexity in cancer development and therapy. Elevated ROS levels can induce metabolic reprogramming and promote the proliferation, invasion, and metastasis of cancer cells, resulting in cancer progression. However, excessive ROS accumulation leads to the occurrence of apoptosis, pyroptosis, necroptosis, and ferroptosis in cancer cells, which restrains tumor development. In the TME, ROS frequently promotes angiogenesis and remodels the extracellular matrix (ECM) by enhancing the differentiation of cancer-associated fibroblasts (CAFs), thereby supporting tumor growth. Concurrently, high ROS levels favour immunosuppressive cells, including M2-polarized macrophages, and regulatory T cells (Tregs), while impairing the antitumor capabilities of T cells. In the aspect of cancer therapy, it is overly simplistic to merely combine chemoradiotherapy with antioxidants as a therapeutic strategy. Instead, highlighting targeted therapies that modulate ROS is essential, given their inherent complexity. Fortunately, a variety of innovative treatments have emerged, including nanodrug delivery systems (NDDS), proteolysis-targeting chimeras (PROTAC), and adoptive cell therapy (ADT), which not only exhibit synergistic effects with immune checkpoint therapy (ICT), but also enhance the antitumor capabilities of the TME. In this paper, we elucidate the mechanism of ROS production, enumerate the role of ROS in cancer development and the TME, and discuss advancements in ROS-targeted cancer therapeutics.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118241"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070185","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":"An N-linked imidazo[1,2-a]pyridine benzoheterobicyclic hybrid inhibits mitosis and cancer cell proliferation by targeting tubulin","authors":"Tuhin Sarkar ,&nbsp;Mehak Sood ,&nbsp;Shweta Shyam Prassanawar ,&nbsp;Kousar Jahan ,&nbsp;Aaditi Kulkarni ,&nbsp;Rushikesh Ahirkar ,&nbsp;Parteek Prasher ,&nbsp;Prasad V. Bharatam ,&nbsp;Dulal Panda","doi":"10.1016/j.bmc.2025.118242","DOIUrl":"10.1016/j.bmc.2025.118242","url":null,"abstract":"<div><div>Colchicine-site agents have strong potential to be used as tubulin-targeted anticancer agents. In this study, a series of imidazo[1,2-<em>a</em>]pyridine-benzoheterobicyclic hybrids linked by a nitrogen atom as <em>N</em>-heterocyclic imines were designed as colchicine site binding agents. Cell-based assays identified two compounds, <strong>6b</strong> (<em>N</em>-(3-(4-chlorophenyl)imidazo[1,2-<em>a</em>](pyridin-2-yl)benzo[<em>d</em>]thiazol-2(3H)-imine) and <strong>6c</strong> (<em>N</em>-(6-chloro-3-phenylimidazo[1,2-<em>a</em>]pyridin-2-yl)-1,3-dihydro-2H-benzo[<em>d</em>]imidazol-2-imine), as the most potent antiproliferative compounds against cervical cancer (HeLa) cells. Compound <strong>6c</strong> inhibited purified tubulin polymerization <em>in vitro</em> and depolymerized microtubules in HeLa and MCF-7 cells. Additionally, <strong>6c</strong> arrested HeLa cells in the mitotic phase, increased the production of reactive oxygen species, and induced cell death. The compound also exhibited a strong binding affinity towards the colchicine binding site on tubulin. Quantum chemical analysis and molecular docking indicated that <strong>6c</strong> preferentially binds to tubulin in its iminic tautomeric state. The chemoinformatic analysis further revealed that <strong>6c</strong> occupies a unique and therapeutically relevant chemical space with a favorable profile regarding physicochemical properties, ADMET, and pharmacokinetics.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118242"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106150","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 thioamide-linked spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV-2","authors":"Samuel Desta Guma ,&nbsp;Kang Song ,&nbsp;Haiguo Sun ,&nbsp;Lei Yang ,&nbsp;Zhaoyin Zhou ,&nbsp;Jin Suo ,&nbsp;Emmanuel Mintah Bonku ,&nbsp;Wei Zheng ,&nbsp;Guanghui Tian ,&nbsp;Xiangrui Jiang ,&nbsp;Qiumeng Zhang ,&nbsp;Yan Zhang ,&nbsp;Jingshan Shen","doi":"10.1016/j.bmc.2025.118239","DOIUrl":"10.1016/j.bmc.2025.118239","url":null,"abstract":"<div><div>A series of thioamide-linked spiropyrrolidine derivatives were synthesized and evaluated against SARS-CoV-2 3CL^pro. Among these compounds, <strong>9g</strong> demonstrated remarkable inhibition of 3CL^pro (IC₅₀ = 35 nM), surpassing the inhibitory potency of the approved antiviral drug nirmatrelvir (IC₅₀ = 54 nM). In cellular assays against HCoV-OC43 in Huh7 cells, <strong>9g</strong> exhibited significant antiviral efficacy (EC₅₀ = 0.52 μM) and low cytotoxicity (CC₅₀ &gt; 10 μM). Furthermore, <strong>9g</strong> exhibited pharmacokinetic profiles comparable to that of nirmatrelvir, making it a promising candidate for further development.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"128 ","pages":"Article 118239"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115759","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}