Bioorganic Chemistry最新文献_第2页

Straightforward synthesis and in silico evaluation of pyrazolylthiazolidinone derivatives as prospective antiproliferative agents 吡唑基噻唑烷酮衍生物作为潜在抗增殖剂的直接合成和硅评价

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109036

Sayed K. Ramadan , Sobhi M. Gomha , Eman A.E. El-Helw

{"title":"Straightforward synthesis and in silico evaluation of pyrazolylthiazolidinone derivatives as prospective antiproliferative agents","authors":"Sayed K. Ramadan , Sobhi M. Gomha , Eman A.E. El-Helw","doi":"10.1016/j.bioorg.2025.109036","DOIUrl":"10.1016/j.bioorg.2025.109036","url":null,"abstract":"<div><div>Cancer remains a leading cause of mortality, underscoring the need for novel agents to improve therapeutic outcomes and overcome drug resistance. Guided by the known antitumor potential of thiazolidinones, a series of arylidene-thiazolidinone derivatives was synthesized <em>via</em> a one-pot cyclocondensation of pyrazolyl-thiosemicarbazone, with chloroacetic acid and aromatic aldehydes. <em>In vitro</em> antiproliferative screening against HCT-116 (colon) and A549 (lung) cancer cell lines identified compounds <strong>3c</strong> (2,4-dihydroxybenzylidene) and <strong>3a</strong> (4-dimethylaminobenzylidene) as the most potent, with stronger activity than the reference drugs doxorubicin and roscovitine, and reduced toxicity toward normal fibroblast (WI-38) cell line. Selectivity index analysis confirmed preferential activity toward cancer cells, suggesting a favorable safety profile. <em>In silico</em> target prediction indicated kinases as probable targets, and docking to EGFR protein (PDB ID: <span><span>3W32</span><svg><path></path></svg></span>) revealed that thiazolidinone <strong>3a</strong> showed the best binding affinity (with appropriate RMSD and good ligand efficiency), forming key π‑hydrogen interactions common with those of the co-crystallized ligand, suggestive of possible EGFR inhibitory activity. ADME predictions further showed favorable gastrointestinal absorption, lipophilicity, oral bioavailability, and drug-likeness for thiazolidinones <strong>3a</strong>, <strong>3b</strong>, and <strong>3</strong> <strong>f</strong>. Collectively, these findings highlight these derivatives as promising scaffolds for further development of antiproliferative therapies.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109036"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217471","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}

引用次数: 0

Optimization of pyrrole-2-carboxamide to develop a potent antituberculosis agent with improved physicochemical property and druggability 优化吡咯-2-羧酸酰胺制备具有较好理化性能和可用药性的强效抗结核药物。

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109016

Yanan Wu , Hongyi Zhao , Bin Wang , Xi Chen , Bo Jin , Yixuan Zheng , Chen Ma , Li Sheng , Yu Lu , Haihong Huang , Dongfeng Zhang

{"title":"Optimization of pyrrole-2-carboxamide to develop a potent antituberculosis agent with improved physicochemical property and druggability","authors":"Yanan Wu , Hongyi Zhao , Bin Wang , Xi Chen , Bo Jin , Yixuan Zheng , Chen Ma , Li Sheng , Yu Lu , Haihong Huang , Dongfeng Zhang","doi":"10.1016/j.bioorg.2025.109016","DOIUrl":"10.1016/j.bioorg.2025.109016","url":null,"abstract":"<div><div>MmpL3, a mycobacterial membrane protein, is essential for the transport of trehalose monomycolate, which is crucial for the formation of the <em>M. tuberculosis</em> outer membrane and the survival of the bacterium. Herein, we optimize our lead MmpL3 inhibitor bearing pyrrole-2-carboxamide scaffold to develop antituberculosis agents with improved physicochemical properties. Compound <strong>27b</strong>, an optimized analog of our lead MmpL3 inhibitor, exhibited enhanced antituberculosis activity along with reduced cytotoxicity, improved microsomal stability, and high Caco-2 permeability. Significantly, the water solubility and pharmacokinetic profile of compound <strong>27b</strong> was markedly improved compared to the lead compound <strong>2</strong>. This compound demonstrated potent efficacy in decreasing the intracellular <em>M. tuberculosis</em> load within mouse macrophages. The results of this study indicated that incorporating an oxygen-containing group in pyrrole-2-carboxamide scaffold can improve the compound's LogP value, thereby achieving a balance between lipophilicity and antituberculosis activity.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109016"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211137","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}

引用次数: 0

Hecogenin‑nitrogen mustard hybrids with improved anti-breast cancer activity: Design, synthesis, and biological evaluation 具有改善抗乳腺癌活性的异源原-氮芥杂交：设计、合成和生物学评价。

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109032

Wenle Su, Xiaoying Huang, Xinyuan Ji, Xinyu Shi, Yixuan Song, Liwei Ma, Wenquan Zhu, Xiaoli Wang, Song Lin, Yukun Ma, Wenbao Wang, Jinling Zhang, Cuiyan Han

{"title":"Hecogenin‑nitrogen mustard hybrids with improved anti-breast cancer activity: Design, synthesis, and biological evaluation","authors":"Wenle Su, Xiaoying Huang, Xinyuan Ji, Xinyu Shi, Yixuan Song, Liwei Ma, Wenquan Zhu, Xiaoli Wang, Song Lin, Yukun Ma, Wenbao Wang, Jinling Zhang, Cuiyan Han","doi":"10.1016/j.bioorg.2025.109032","DOIUrl":"10.1016/j.bioorg.2025.109032","url":null,"abstract":"<div><div>To enhance the efficacy of hecogenin (HCG) against breast cancer cells, we designed and synthesized two series of new HCG‑nitrogen mustard hybrids (<strong>4a</strong>–<strong>4f</strong> and <strong>5a</strong>–<strong>5f</strong>) by linking benzoic acid mustard or chlorambucil to HCG via amino acid residues. The derivatives were screened to assess their anti-proliferative activity against three human breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7), and one normal human breast MCF-10A cell line. Among the synthesized compounds, hybrid <strong>5d</strong> exhibited the most potent anti-proliferative activity against the triple-negative breast cancer cell line MDA-MB-231, with an IC<sub>50</sub> value of 2.2 μM. This represents a 27.2-fold increase in potency compared to the parent compound HCG (IC<sub>50</sub> = 59.8 μM). Furthermore, hybrid <strong>5d</strong> exhibited low toxicity toward MCF-10A cells (IC<sub>50</sub> > 100 μM), indicating certain selectivity. Notably, the transwell migration assay revealed that hybrid <strong>5d</strong> significantly inhibited the invasion of MDA-MB-231 cells. Preliminary mechanism studies indicated that hybrid <strong>5d</strong> induced G2/M phase arrest and apoptosis via the mitochondria-related apoptotic pathway, as well as caused DNA damage. Collectively, these results suggest that hybrid <strong>5d</strong> is a promising lead compound for anti-breast cancer research worthy of further investigation.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109032"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243364","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}

引用次数: 0

Probiotic-based derived exopolysaccharide-zinc oxide nanoparticles: a novel approach to colorectal cancer gene modulation 基于益生菌衍生的胞外多糖氧化锌纳米颗粒：一种结肠癌基因调节的新方法。

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109025

Saeideh Afsharipoor , Razieh Nazari , Anoosh Eghdami , Mahdi Fasihi-Ramandi , Mohammad Reza Zolfaghari

{"title":"Probiotic-based derived exopolysaccharide-zinc oxide nanoparticles: a novel approach to colorectal cancer gene modulation","authors":"Saeideh Afsharipoor , Razieh Nazari , Anoosh Eghdami , Mahdi Fasihi-Ramandi , Mohammad Reza Zolfaghari","doi":"10.1016/j.bioorg.2025.109025","DOIUrl":"10.1016/j.bioorg.2025.109025","url":null,"abstract":"<div><div>The second deadliest cancer in the world is colorectal cancer (CRC), which is caused by the uncontrolled proliferation of epithelial cells in the colon. This research examines the role of key genes—including tumor suppressors <em>ING4</em> and <em>APC</em>, angiogenesis-related <em>DHX32</em>, and the oncogenic mutated <em>P53</em>—in the SW480 cell line. Probiotics and their exopolysaccharide (EPS) component show potential in cancer prevention and treatment due to their antioxidant and anti-cancer properties. Zinc oxide nanoparticles (ZnONPs), recognized for their unique physical and chemical characteristics, have broad applications in drug delivery, cancer diagnostics, and therapy. In this project, EPS was extracted from <em>Lactiplantibacillus plantarum</em> and used for ZnONPs biosynthesis, followed by characterization through UV–VIS, XRD, FTIR, FE-SEM, and zeta potential analysis. Cytotoxic effects of EPS and ZnONPs were evaluated on SW480 cells, along with their antioxidant properties. Quantitative real-time PCR analysis revealed decreased expression of <em>DHX32</em> and <em>P53</em>, while <em>ING4</em> and <em>APC</em> gene expression increased following treatment of the cancerous cell line with target agents. These findings suggest that probiotic-derived EPS and ZnONPs may offer effective strategies for CRC treatment by modulating critical gene expression involved in disease progression.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109025"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211111","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}

引用次数: 0

A versatile synthetic approach to various 5-alkynyl modified isatin derivatives: Cytotoxicity, acetylcholinesterase inhibition activity and molecular modeling study 各种5-炔基修饰的isatin衍生物的合成方法：细胞毒性、乙酰胆碱酯酶抑制活性和分子模型研究。

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109038

Kirill P. Cheremnykh , Igor D. Ivanov , Mohammad S. Hamad , Andrey I. Khlebnikov , Victor A. Savelyev , Mikhail A. Pokrovsky , Andrey G. Pokrovsky , Elvira E. Shults

{"title":"A versatile synthetic approach to various 5-alkynyl modified isatin derivatives: Cytotoxicity, acetylcholinesterase inhibition activity and molecular modeling study","authors":"Kirill P. Cheremnykh , Igor D. Ivanov , Mohammad S. Hamad , Andrey I. Khlebnikov , Victor A. Savelyev , Mikhail A. Pokrovsky , Andrey G. Pokrovsky , Elvira E. Shults","doi":"10.1016/j.bioorg.2025.109038","DOIUrl":"10.1016/j.bioorg.2025.109038","url":null,"abstract":"<div><div>Isatin derivatives have been of great interest in drug development research. 5-Alkynyl substituted isatin derivatives with anticancer potential and acetylcholinesterase inhibition (AChE) activity are designed and synthesized. The copper(I) catalyzed one-pot three-component reaction (AChauhan et al. (2021)<sup>3</sup>-coupling) of new 3-(1,3-dioxolane)-5-(ethynyl)isatins with formaldehyde and secondary amines or the Sonogashira cross-coupling reaction of C-3 protected iodoisatins with fluoro-N-(prop-2-ynyl)benzamide and prop-2-ynyl 4-fluorobenzoate were the main approaches for the synthesis of 5-(3-X-prop-1-yn-1-yl) substituted isatin derivatives (yield 53–87 %). 1-Benzyl-5-(prop-1-yn-1-yl)indoline-2,3-diones are smoothly formed by refluxing of 3-(1,3-dioxolane)-5-(propynyl)isatins in hydrochloric acid/MeOH (1:9, <em>v</em>/v). Results of <em>in vitro</em> biological assays (MTT-test) revealed that new 3-(1,3-dioxolane)-5-(3-X-prop-1-yn-1-yl)-1-benzylisatin derivatives are exhibited remarkable cytotoxicity against human cervical (C 33 A and CaSki), breast (MCF-7), prostate (DU-145) and glioblastoma (SNB-19 and T98G) cancer cell lines within low micromolar GI<sub>50</sub> values. Additionally, all new compounds demonstrated relatively low cytotoxicity against the normal epithelial VERO cells (GI<sub>50</sub> > 70 μM), indicating good selectivity. Moreover, the appropriate isatin derivatives displayed good and moderate acetylcholinesterase inhibition activity <em>in vitro</em> (Ellman’ s method) with IC<sub>50</sub> up to 1.0–3.7 μM comparable to that for clinically used galantamine. Based on the results of <em>in silico</em> experiments the isatin derivatives bearing 5-(prop-1-yn-1-yl) substituents are promising for further search of acetylcholinesterase inhibitors in this series of compounds.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109038"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211166","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}

引用次数: 0

Discovery and evaluation of pyrimidine-2,4-dione derivatives as novel SARS-CoV-2 Mpro inhibitors with antiviral effect 嘧啶-2,4-二酮衍生物作为新型抗病毒SARS-CoV-2 Mpro抑制剂的发现和评价

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109026

Zixuan Rao , Linyi Yu , Zhenhao Tang , Shun Liu , Shunjing Wang , Li Zhao , Yihang Zhong , Wei Peng , Qingqing Zhang , Wei Zhang , Xupeng Huang , Man Liu

{"title":"Discovery and evaluation of pyrimidine-2,4-dione derivatives as novel SARS-CoV-2 Mpro inhibitors with antiviral effect","authors":"Zixuan Rao , Linyi Yu , Zhenhao Tang , Shun Liu , Shunjing Wang , Li Zhao , Yihang Zhong , Wei Peng , Qingqing Zhang , Wei Zhang , Xupeng Huang , Man Liu","doi":"10.1016/j.bioorg.2025.109026","DOIUrl":"10.1016/j.bioorg.2025.109026","url":null,"abstract":"<div><div>The COVID-19 pandemic has underscored the persistent threat of zoonotic coronavirus transmission to global health. In this study, we targeted the clinically validated SARS-CoV-2 main protease (M<sup>pro</sup>) and implemented a scaffold-hopping strategy to design and synthesize 32 pyrimidine-2,4-dione derivatives, aiming to explore underutilized interactions within the S1, S1’, and S2 subpockets. Structure–activity relationship (SAR) analysis identified compound <strong>17</strong> as a potent M<sup>pro</sup> inhibitor (IC<sub>50</sub> = 21.1 nM) with outstanding antiviral activity against the SARS-CoV-2 JN.1 variant (EC<sub>50</sub> < 2 nM). Furthermore, X-ray crystallography of the M<sup>pro</sup>–compound <strong>15</strong> complex unveiled a previously unreported T-shaped π-π interaction between the P1’-phenyl ring and His41. These results demonstrate the effectiveness of structure-based optimization of the pyrimidine-2,4-dione scaffold for the development of novel coronavirus M<sup>pro</sup> inhibitors.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109026"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216856","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}

引用次数: 0

A chemotherapy based on dual-targeted release of ciprofloxacin in mitochondrial and endoplasmic reticulum 基于线粒体和内质网双靶向释放环丙沙星的化疗

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109068

Xuan Wang , Yan-Ping Liu , Chong-Yang Wang , Ming-Hua Zheng , Jing-Yi Jin

{"title":"A chemotherapy based on dual-targeted release of ciprofloxacin in mitochondrial and endoplasmic reticulum","authors":"Xuan Wang , Yan-Ping Liu , Chong-Yang Wang , Ming-Hua Zheng , Jing-Yi Jin","doi":"10.1016/j.bioorg.2025.109068","DOIUrl":"10.1016/j.bioorg.2025.109068","url":null,"abstract":"<div><div>Organelle-targeting drugs represent the next generation of precision chemotherapy. To achieve this, a specific organelle-targeting group is essential for various nano-medicines and prodrugs. Simultaneously targeting multiple organelles enhances drug efficacy by enabling lower dosage, minimizing side effects, and potentially altering the action mechanism of drugs through synchronous effects across organelles. However, designing a molecular platform capable of delivering drugs to multiple organelles remains challenging, which hinders the advancement of precise chemotherapy. Here, we conjugated a pyronine unit as a warhead to an antibiotic (ciprofloxacin, Cip) <em>via</em> a covalent linkage, developing a molecular platform termed CPY. This platform simultaneously targets mitochondria (Mito) and the endoplasmic reticulum (ER), releasing Cip <em>in situ</em> through a glutathione-mediated S<sub>N</sub>Ar pathway. CPY induced apoptosis in tumor cells and exhibited anti-tumor activity in a xenograft tumor model. These results demonstrate a feasible strategy for repurposing conventional non-antitumor drugs into chemotherapeutic agents.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109068"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217472","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}

引用次数: 0

Sesquiterpenoids from Eupatorium chinense L. induce G0/G1 cell cycle arrest and apoptosis in AGS cell via DNA-PK/AKT/p53 pathway 泽兰倍半萜类化合物通过DNA-PK/AKT/p53通路诱导AGS细胞G0/G1细胞周期阻滞和凋亡

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109059

Han-Chuan Wang , Yu-Qi Shi , Bing-Hang Ji, Zhu-Ling-Zhi Kuang, Ce Song, Wen-Zhuo Ming, Yu-Meng Wang, Da-Li Meng

{"title":"Sesquiterpenoids from Eupatorium chinense L. induce G0/G1 cell cycle arrest and apoptosis in AGS cell via DNA-PK/AKT/p53 pathway","authors":"Han-Chuan Wang , Yu-Qi Shi , Bing-Hang Ji, Zhu-Ling-Zhi Kuang, Ce Song, Wen-Zhuo Ming, Yu-Meng Wang, Da-Li Meng","doi":"10.1016/j.bioorg.2025.109059","DOIUrl":"10.1016/j.bioorg.2025.109059","url":null,"abstract":"<div><div>Ten undescribed sesquiterpenes, including 5 undescribed guaiane-type sesquiterpenes (<strong>1–5</strong>) and 5 undescribed gemmarane-type sesquiterpenes (<strong>6–10</strong>), along with fourteen known analogues (<strong>11–24</strong>) were isolated from the whole plants of <em>Eupatorium chinense</em> L. They structures were determined by interpretation of spectroscopic data (UV, NMR, ECD, HRESIMS, and DP4+). The cytotoxicity of sesquiterpene derivatives (<strong>1–24)</strong> was evaluated against five human cancer cell lines (Hep<img>3B, A549, AGS, MCF-7, and HCT-116). Among these, compound <strong>1</strong> exhibited the most potent cytotoxic activity against the gastric adenocarcinoma AGS cell line, with an IC<sub>50</sub> value of 4.33 μM. Mechanistic studies revealed that compound <strong>1</strong> suppresses the DNA-PK/AKT/p53 signaling pathway in AGS cells. Concomitantly, it upregulates p21 protein expression while downregulating CDK4 and cyclin D protein levels, inducing G<sub>0</sub>/G<sub>1</sub> phase cell cycle arrest. Furthermore, compound <strong>1</strong> promotes apoptosis by increasing Bax expression and decreasing Bcl-2 expression. Collectively, these findings establish compound <strong>1</strong> as a promising lead candidate for the development of novel anti-gastric cancer therapeutics.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109059"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217475","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}

引用次数: 0

68Ga-DOTA-Neratinib: A novel small-molecule PET tracer for breast cancer imaging 68Ga-DOTA-Neratinib：一种用于乳腺癌成像的新型小分子PET示踪剂。

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109031

Shangjing Pang , Yuanzhuo Yan , Hongyin Ding , Die You , Chunfang Zhang , Min Tan , Yue Chen

{"title":"68Ga-DOTA-Neratinib: A novel small-molecule PET tracer for breast cancer imaging","authors":"Shangjing Pang , Yuanzhuo Yan , Hongyin Ding , Die You , Chunfang Zhang , Min Tan , Yue Chen","doi":"10.1016/j.bioorg.2025.109031","DOIUrl":"10.1016/j.bioorg.2025.109031","url":null,"abstract":"<div><div>Current DOTA-based <sup>68</sup>Ga-labeled small-molecule probes targeting HER2 often suffer from limited tumor-specific uptake. To overcome this limitation, we selected Neratinib, a second-generation pan-HER tyrosine kinase inhibitor, and successfully developed a novel PET imaging agent, <sup>68</sup>Ga-DOTA-Neratinib. The probe demonstrated high radiochemical yield, excellent in vitro and in vivo stability, and strong binding affinity for the HER2 receptor. Cell uptake assays confirmed specific accumulation in HER2-positive cell lines: uptake in BT-474 and SK-BR-3 cells at 2 h post-incubation was 7.55 ± 1.10 % and 8.18 ± 0.56 %, respectively, significantly higher than that in HER2-negative MCF-7 cells (4.71 ± 0.79 %, <em>P</em> < 0.05). Moreover, micro-PET/CT imaging in HER2-positive tumor-bearing mice showed enhanced tumor uptake and prolonged intratumoral retention of the tracer, though some background blood activity was also observed. These findings suggest that <sup>68</sup>Ga-DOTA-Neratinib is a promising small-molecule PET probe for the noninvasive imaging of HER2-positive breast cancer.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109031"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211149","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}

引用次数: 0

Novel 4-quinolone derivative inflicted cytotoxicity via intrinsic apoptotic pathway activation on human metastatic triple-negative breast cancer cells 新型4-喹诺酮衍生物通过内在凋亡通路激活对人转移性三阴性乳腺癌细胞施加细胞毒性

IF 4.7 2区医学

Bioorganic Chemistry Pub Date : 2025-10-01 DOI: 10.1016/j.bioorg.2025.109033

Nursyuhada Azzman , Muhammad Shoaib Ali Gill , Nurshariza Abdullah , Denisse A. Gutierrez , Armando Varela-Ramirez , Laura A. Sanchez-Michael , Jose A. Lopez-Saenz , Mohamad Nurul Azmi Mohamad Taib , Syed Adnan Ali Shah , Renato J. Aguilera , Nafees Ahemad

{"title":"Novel 4-quinolone derivative inflicted cytotoxicity via intrinsic apoptotic pathway activation on human metastatic triple-negative breast cancer cells","authors":"Nursyuhada Azzman , Muhammad Shoaib Ali Gill , Nurshariza Abdullah , Denisse A. Gutierrez , Armando Varela-Ramirez , Laura A. Sanchez-Michael , Jose A. Lopez-Saenz , Mohamad Nurul Azmi Mohamad Taib , Syed Adnan Ali Shah , Renato J. Aguilera , Nafees Ahemad","doi":"10.1016/j.bioorg.2025.109033","DOIUrl":"10.1016/j.bioorg.2025.109033","url":null,"abstract":"<div><div>Quinolones are a class of compounds that have shown promising potential as anticancer agents. However, the current quinolones in clinical trials are currently hampered by their efficacy issues. Therefore, we designed and synthesized novel 4-quinolone-3-carboxamide derivatives <strong>14–67</strong>. All the synthesized compounds were initially screened for their cytotoxicity activity using the MTT assay method and evaluated for their anticancer activities against leukemia and breast cancer cells using the Differential Nuclear Staining (DNS) assay. Six screened compounds exhibited low CC<sub>50</sub> inhibitory effects against breast cancer cell lines, where compounds <strong>24, 25, 52,</strong> and <strong>65</strong> also showed good activity (CC<sub>50</sub> = 6.99–11.17 μM) against the leukemia cell line (Jurkat). In vitro assessment showed that the most active compound, <strong>65,</strong> exhibited significantly higher growth inhibition activity (CC<sub>50</sub> = 7.10–83.2 μM) in breast cancer cell lines, with less cytotoxicity observed in non-cancerous cells (MCF-10 A). The most active analog, compound <strong>65,</strong> triggered apoptosis via membrane depolarization and caused cell cycle arrest at the S phase in the MDA-MB231/LM2-4 cell line. In conclusion, the outcomes indicate that compound <strong>65</strong> exhibits the potential to be a potent and effective anticancer agent, making it an excellent candidate for further research and development.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"165 ","pages":"Article 109033"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216859","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}

引用次数: 0