Bioorganic & Medicinal Chemistry最新文献

{"title":"Corrigendum to “Discovery of N-(4-(pyridin-4-yloxy)phenyl)-1,2-dihydropyridine-3-carboxamide derivatives as potential type II c-Met inhibitors” [Bioorg. Med. Chem. 131 (2025) 118394]","authors":"Qingwang Xin , Chao Fang , Baojian Xing , Jikang Du , Simin Ren","doi":"10.1016/j.bmc.2025.118524","DOIUrl":"10.1016/j.bmc.2025.118524","url":null,"abstract":"","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118524"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802901","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":"The development of anti-HIV agents targeting APOBEC3G/Vif axis","authors":"Qiqi Bao ,&nbsp;Jiajia Wen ,&nbsp;Fengjiao Xiang ,&nbsp;Ling Ma ,&nbsp;Jiwei Ding ,&nbsp;Xinlu Wang ,&nbsp;Shan Cen ,&nbsp;Jinming Zhou","doi":"10.1016/j.bmc.2025.118519","DOIUrl":"10.1016/j.bmc.2025.118519","url":null,"abstract":"<div><div>The human host restriction factor APOBEC3G (Apolipoprotein B mRNA editing enzyme-catalytic polypeptide-like 3G, A3G) potently inhibits the replication of human immunodeficiency virus type 1 (HIV-1). To counteract this restriction, HIV-1 encodes the viral infectivity factor (Vif), which mediates the degradation of A3G and thereby abrogates A3G's antiviral activity. Previously, we identified IMB-301 via virtual screening coupled with biological validation, which protects A3G from Vif-induced degradation through binding specifically to A3G, thereby preserving A3G's deaminase activity to suppress HIV-1 replication. Herein, we performed structural optimization of IMB-301, yielding a library of 64 analogs. Most of these analogs retained HIV-1 inhibitory activity, with several exhibiting significantly enhanced potency relative to IMB-301. Further investigations demonstrated that these active analogs block the Vif-A3G interaction, restore intracellular A3G levels, and ultimately inhibit HIV-1 proliferation in an A3G-dependent manner. Collectively, this work highlights a promising avenue for the development of novel anti-HIV-1 therapeutic strategies and candidate molecules.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118519"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789205","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":"Novel PROTACs with polyhedral alkanes as linkers for enhanced ALK degradation in drug-resistant NSCLC","authors":"Dongchen Chu ,&nbsp;Huijie Han ,&nbsp;Chaochun Wei ,&nbsp;Xiaokun Zhang ,&nbsp;Hong Yan ,&nbsp;Juan Wang","doi":"10.1016/j.bmc.2025.118521","DOIUrl":"10.1016/j.bmc.2025.118521","url":null,"abstract":"<div><div>The challenge of overcoming drug-resistant mutations in Anaplastic Lymphoma Kinase (ALK), a critical driver of non-small cell lung cancer (NSCLC), remains a pressing clinical concern. This study introduces a novel approach by using polyhedral alkanes as linkers in PROTAC (Proteolysis Targeting Chimera) technology to address resistance mechanisms. Unlike conventional chain-like or planar linkers, five novel ALK-targeting PROTACs (BL-1-BL-5) featuring structurally unique polyhedral alkanes (cubane, homocubane, adamantane, <em>D</em>_<em>3</em>-trihomocubane and norbornene) were designed and synthesized through innovative HAPOD trail and organic synthesis methodologies. Comprehensive <em>in vitro</em> evaluations revealed remarkable antiproliferative activity across all derivatives, with BL-5 (norbornene as linker) demonstrating exceptional potency (<em>IC₅₀</em> = 36.21 nM) against H3122 cells, surpassing both reference SIAIS164018 (BB-1, <em>IC₅₀</em> = 78.93 nM) and Brigatinib (<em>IC₅₀</em> = 44.83 nM). Western blot assay confirmed that BL-5 effectively degraded ALK at 100 nM concentration while effectively inhibiting ALK phosphorylation. Notably, BL-5 exhibited superior efficacy against Ba/F3 cells with the ALK G1202R resistance mutation (<em>IC</em>_<em>50</em> = 118.86 nM) compared to BB-1 (<em>IC₅₀</em> = 126.41 nM). MD simulations provided critical insights, revealing that the BL-1, BL-4 and BL-5 significantly enhanced the ternary complex stability compared to traditional linkers. These findings establish the polyhedral alkanes as novel linkers in PROTAC design, with BL-5 emerging as a particularly promising candidate for targeting ALK.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118521"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789206","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":"Computationally guided design of N4-(2-methyl-2H-indazol-6-yl)-N2-phenylpyrimidine-2,4-diamine inhibitors of EGFR kinase targeting Cys797","authors":"Adchata Konsue ,&nbsp;Duangkamol Gleeson ,&nbsp;Kiattawee Choowongkomon ,&nbsp;Donald J.L. Jones ,&nbsp;Pimkhuan Hannanta-anan ,&nbsp;Robert G. Britton ,&nbsp;M. Paul Gleeson","doi":"10.1016/j.bmc.2025.118544","DOIUrl":"10.1016/j.bmc.2025.118544","url":null,"abstract":"<div><div>The epidermal growth factor receptor kinase (EGFR) is a tyrosine kinase (TK) implicated in the uncontrolled growth of non-small cell lung cancer. EGFR-TK inhibitors have been used extensively, however inhibitor resistance often develops leading to disease progression. In this work, we report the computationally guided design and preparation of novel covalent 2,4-diaminopyrimidine EGFR-TK inhibitors, inspired by Osimertinib. Molecular dynamics simulations and quantum mechanical (QM) calculations were performed on novel designs incorporating a 2-methyl-2<em>H</em>-indazol-6-amine at the 4-position of pyrimidine as well as various linkers and electrophiles. Calculations suggested swapping the 5-pyrimidine <img>H atom for <img>Cl would lead to a preferential “out” ligand conformation that favored T790M enzyme which was later confirmed experimentally. Compound <strong>19</strong> was the most potent inhibitor of WT EGFR (3.0 nM) observed, more potent than the EGFR WT inhibitor Erlotinib (5.9 nM). Compounds <strong>48</strong> and <strong>49</strong> demonstrated better activity for the double-mutant EGFR (3.0 &amp; 2.0 nM, respectively) than Osimertinib (12.8 nM). The selectivity of these compounds for the DM was found to be comparable to Osimertinib (∼20 fold) while their phosphate buffer solubilities were &gt; 50-fold better than both marketed drugs. Kinetic evaluation of <strong>48</strong> (propenamide moiety) vs <strong>49</strong> (acrylamide electrophile) confirms k_inact/K_i values consistent with a covalent mode of action for the latter, but not the former.</div><div>2009 Elsevier Ltd. All rights reserved.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118544"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922075","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":"Targeting HPK1 for cancer immunotherapy: An update on recent medicinal chemistry advances","authors":"Yiyun Song ,&nbsp;Zepeng Liao ,&nbsp;Xiang Ni ,&nbsp;Dexiang Wang,&nbsp;Zhihao Qi,&nbsp;Qi Miao,&nbsp;Sheng Jiang,&nbsp;Kuojun Zhang","doi":"10.1016/j.bmc.2026.118546","DOIUrl":"10.1016/j.bmc.2026.118546","url":null,"abstract":"<div><div>Hematopoietic progenitor kinase 1 (HPK1), a pivotal negative regulator of immune signaling pathways, represents an attractive therapeutic target for cancer immunotherapy. Supported by encouraging preliminary clinical data showing promising efficacy and manageable safety profiles in clinical trials, the rapid development of structurally diverse small-molecule HPK1 inhibitors continues. However, achieving high selectivity for HPK1 remains challenging due to significant sequence homology among the related kinase family. Emerging evidence also implicates HPK1's non-catalytic scaffolding function in tumor immune regulation, complicating traditional inhibition strategies. Notably, PROteolysis-TArgeting Chimeras (PROTAC) technology offers distinct advantages for targeting HPK1, driving significant momentum in the development of novel HPK1 PROTACs. This article provides a comprehensive update on recent advances in HPK1-targeted therapeutics, highlighting key progress in the evolution of structurally distinct small-molecule HPK1 inhibitors with improved selectivity, ADME and safety profiles, the development and pharmacological outcomes of HPK1-targeted PROTACs, as well as translational progress of clinical-stage candidates. Finally, we discuss future perspectives and challenges in this rapidly evolving field.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118546"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916284","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":"Luminescent dihydroquinolines: fluorescence in aqueous media and insights into anticancer activity","authors":"Lidiane Gomes de Araújo ,&nbsp;Rafael Gomes Soares ,&nbsp;Bruno Galdino Lopes ,&nbsp;Ana Rita de Sousa França ,&nbsp;Karen Isabelly Santos Cardoso Brandão ,&nbsp;Edilson Beserra de Alencar Filho ,&nbsp;Yuri Virgílio dos Santos ,&nbsp;Gardenia Carmen Gadelha Militão ,&nbsp;Claudio Gabriel Lima-Junior ,&nbsp;Rodrigo Cristiano","doi":"10.1016/j.bmc.2025.118528","DOIUrl":"10.1016/j.bmc.2025.118528","url":null,"abstract":"<div><div>Two dihydroquinoline derivatives were synthesized through a modified Doebner reaction, which resulted in stable dihydroquinolines instead of the expected aromatized products. Their photophysical properties were investigated in solution, in the solid state, and in aqueous media, and their anticancer potential was evaluated. Both derivatives exhibited fluorescence and moderate cytotoxicity toward the HL-60 leukemia cell line. Quantum chemical calculations combined with the analysis of experimental ¹H NMR shifts confirmed the formation of an intramolecular hydrogen bond (IHB) in the compound bearing an <em>ortho</em>-phenolic hydroxy group, which appears to reduce its affinity for biological targets. Molecular docking studies on common quinoline-associated targets suggested that both derivatives may act as tubulin depolymerizers and DNA intercalators. Interestingly, both compounds exhibited aggregation-induced emission (AIE), with the unsubstituted derivative exhibiting unusual solvent-dependent luminescence and stable emission near physiological pH. Overall, these findings identify dihydroquinolines as promising luminescent scaffolds with tunable optical behavior and preliminary anticancer activity, providing a foundation for future structural optimization and biological studies.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118528"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814956","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 a focused pyrrolo- and pyrido-quinazolinone natural products-templated library for anti-fungal and anthelmintic activities","authors":"Romina E. D'Almeida ,&nbsp;Paulina Chen ,&nbsp;Yanchang Huang ,&nbsp;Emily Goetz ,&nbsp;Vamshikrishna Reddy Sammeta ,&nbsp;Bo Yang ,&nbsp;Reeta P. Rao ,&nbsp;Sivappa Rasapalli ,&nbsp;Mostafa A. Elfawal","doi":"10.1016/j.bmc.2025.118517","DOIUrl":"10.1016/j.bmc.2025.118517","url":null,"abstract":"<div><div>A focused pyrrolo- and pyrido-quinazoline natural products-templated library has been designed and synthesized using two novel synthetic approaches: an aza-Nazarov approach and a Dieckmann cyclization strategy. This privileged scaffold-based collection was screened against pathogenic fungi and parasitic helminths. Three compounds (<strong>23b, 25a, 13f</strong>) emerged as potent inhibitors of <em>Candida auris</em> adhesion, each causing more than 50 % inhibition at 10 μM, and two compounds (<strong>13k, 14h</strong>) displayed strong anthelmintic activity, demonstrating 7- to 28-fold enhanced activity against human hookworms relative to albendazole. These molecules represent promising leads for the design and synthesis of focused quinazolinone analogs to support SAR driven optimization against <em>C. auris</em> or helminth pathogens. Ongoing efforts aim to refine these bioactive leads by improving their pharmacokinetic and activity profiles through targeted structural modifications.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118517"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838166","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 and optimization of novel and potent allosteric HIV-1 integrase inhibitors with a spiro[indene] moiety","authors":"Kaoru Adachi,&nbsp;Tomoyuki Manabe,&nbsp;Takayuki Yamasaki,&nbsp;Akira Suma,&nbsp;Yosuke Ogoshi,&nbsp;Akihiko Takahashi,&nbsp;Takuya Orita,&nbsp;Akihiro Nomura,&nbsp;Tsuyoshi Adachi,&nbsp;Yoshitsugu Ohata,&nbsp;Yoshiyuki Akiyama,&nbsp;Susumu Miyazaki","doi":"10.1016/j.bmc.2025.118526","DOIUrl":"10.1016/j.bmc.2025.118526","url":null,"abstract":"<div><div>Allosteric inhibitors of HIV-1 integrase offer a promising approach to block an essential process in HIV-1 replication and offer a new strategy for HIV treatment. During the course of our drug discovery investigations, we identified novel allosteric HIV-1 integrase inhibitor <strong>1</strong> which has a conformationally constrained spiro indane scaffold. Our subsequent medicinal chemistry efforts using a structure-based drug design focused on the efficacies of related compound <strong>5</strong> against not only the wild type enzyme but also enzymes with polymorphisms and resistance mutations. As a result, we identified compound <strong>38</strong> <strong>f</strong>, which exhibited the desired efficacy against major polymorphisms and resistance mutations (EC₅₀(WT) = 0.0040 μM, EC₅₀(T124N) = 0.0048 μM, EC₅₀(T125A) = 0.0038 μM, EC₅₀(A128T) = 0.0057 μM), potent anti-HIV activity in the human serum assay (EC₅₀(HS50%) = 0.091 μM), and preferable PK profiles in rats (Cl_tot = 0.017 L/h/kg, MRT = 12.5 h, BA = 71.4 %).</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118526"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808885","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":"Synthesis and evaluation of novel 4-thiazolidinone-5-nitrofuran hybrids as promising antimicrobial agents","authors":"Volodymyr Horishny ,&nbsp;Dmytro Mural ,&nbsp;Iryna Kovalenko ,&nbsp;Nataliya Finiuk ,&nbsp;Iryna Ivasechko ,&nbsp;Yulian Konechnyi ,&nbsp;Iryna Tymchuk ,&nbsp;Stepan Nedzelskyi ,&nbsp;Yuliia Kozak ,&nbsp;Tetyana Rumynska ,&nbsp;Krzysztof Niemczuk ,&nbsp;Monika Szymańska-Czerwińska ,&nbsp;Victoriya Georgiyants ,&nbsp;Rostyslav Stoika ,&nbsp;Roman Lesyk ,&nbsp;Serhii Holota","doi":"10.1016/j.bmc.2026.118545","DOIUrl":"10.1016/j.bmc.2026.118545","url":null,"abstract":"<div><div>Searching for new effective small molecules targeting resistant strains of microorganisms is an emerging task for modern medicinal chemistry. Taking into account potential antimicrobial features of 4-thiazolidinone and 5-nitrofurane pharmacophores, two series of hybrid molecules were synthesized based on 5-nitrofuran-2-carbaldehyde, bioisosteric <em>(E)</em>-3-(5-nitrofuran-2-yl)acrylaldehyde, and structure-modified 4-thiazolidinone scaffolds. For all synthesized compounds, antimicrobial activity screening and cytotoxicity evaluation were performed. Novel highly active hybrid molecules with a low level of toxicity were identified, showing high broad-spectrum activity towards Gram-positive and Gram-negative bacteria, fungi, in particular <em>Staphylococcus aureus</em>, <em>Klebsiella pneumoniae</em>, <em>Corynebacterium diphtheriae</em>, and <em>Aspergillus niger</em>. A preliminary SAR analysis was performed, and key structural features that influence the manifestation of antimicrobial activity were highlighted. The obtained results will contribute to the rational design of novel agents of this pharmacological profile among 4-thiazolidinone-5-nitrofuran hybrids and related heterocyclic molecules.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"134 ","pages":"Article 118545"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916291","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":"Novel benzoxazole-based hybrids as multi-target inhibitors of aromatase, EGFR, and PI3K with potential anti-breast cancer activity","authors":"Mai S. El-Shoukrofy ,&nbsp;Mai E. Amr ,&nbsp;Tarek M. Okda ,&nbsp;A.-Mohsen M.E. Omar ,&nbsp;Omaima M. AboulWafa","doi":"10.1016/j.bmc.2025.118477","DOIUrl":"10.1016/j.bmc.2025.118477","url":null,"abstract":"<div><div>Novel anti-breast cancer benzoxazoles were synthesized applying the scaffold hopping and molecular hybridization approaches. MTT assay showed that <strong>6</strong> and <strong>9b</strong> were 4.5 and 2 times more potent than doxorubicin against MCF-7 cells, while <strong>9a</strong> and <strong>13b</strong> were 10 and 7.5 times more effective against MDA-MB-231 cells, respectively. The four compounds showed good safety profiles toward MCF-10A cells' growth. Enzyme inhibition assays identified <strong>9b</strong> as a potent aromatase (ARO) inhibitor, exhibiting twice the potency of letrozole. <strong>13d</strong> was more potent PI3Kα inhibitor than pictilisib, while <strong>6, 9a,</strong> and <strong>13b</strong> were multi-kinase inhibitors. Compound <strong>9a</strong> was 2 and 2.5 times more potent than lapatinib against EGFR^WT and EGFR^L858R, besides being a selective PI3Kα/β inhibitor, surpassing pictilisib by 3 and 1.5 times, respectively. Compound <strong>13b</strong> exhibited comparable EGFR^L858R inhibition to lapatinib and outperformed pictilisib against PI3Kα, PI3Kβ, and PI3Kδ. Compound <strong>6</strong> showed greater ARO inhibition than letrozole, while being slightly less potent than pictilisib against PI3Kα and PI3Kβ. The four compounds downregulated p-ERK and/or p-AKT levels more effectively than letrozole or lapatinib. They elevated Beclin-1 levels and increased caspase-9 levels with <strong>6, 9a</strong> and <strong>9b</strong> inducing higher %total apoptosis than doxorubicin in annexin V/ propidium iodide assay. Moreover, <strong>9a</strong> reduced cell migration and invasion percentages to 9.22 and 16.95 %, respectively, in MDA-MB-231-treated cells, thereby suppressed metastasis. Docking studies supported the <em>in vitro</em> enzymatic inhibition assays results. Thus, <strong>9b</strong> and <strong>13d</strong> are potent anti-breast cancer benzoxazoles with selective ARO and PI3kα inhibition activity, respectively, while <strong>6, 9a,</strong> and <strong>13b</strong> are multi-target inhibitors exhibiting other anticancer synergistic mechanisms.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"133 ","pages":"Article 118477"},"PeriodicalIF":3.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676001","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}