European Journal of Medicinal Chemistry最新文献

{"title":"Discovery of A Potent Anticancer Agent against Pancreatic Ductal Adenocarcinoma Targeting FAK with DFG-out State and JAK/Aurora Kinases","authors":"Rong-Hong Zhang, Ting Chen, Qian-Qian Xiong, Shan Wang, Guo-Qi Chen, Wen-Li Zhang, Hong-Fei Yuan, Yong-Long Zhao, Ting Liu, Yong Huang, Meng Zhou, Cheng-Li Yang, Shang-Gao Liao, Yong-Jun Li","doi":"10.1016/j.ejmech.2024.117059","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117059","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer because of the difficulty in diagnosis and its resistance to chemotherapy. Focal adhesion kinase (FAK) is found overexpressed in PDAC, and targeting FAK has been proved to impede the progress of PDAC. However, most of FAK inhibitors were reported to bind with FAK in a DFG-in conformation, leading to a limited anti-tumor effect in clinical studies. Herein, to develop FAK inhibitors targeting the inactive DFG-out conformation, a series of large aromatic rings were selected to improve the interaction with Phe565 of the DFG motif. Compound <strong>26</strong> was designed to effectively inhibit FAK and the proliferation of PANC-1 cells with IC₅₀ of 50.94 nM and 0.15 μM, respectively. Besides, compound <strong>26</strong> was proved to strongly suppress the proliferation, colony formation, migration, and invasion in FAK-overexpressing PDAC cells. This inhibitor was confirmed to induce the apoptosis and G2/M arrest in PANC-1 cells through the suppression of FAK/PI3K/Akt signal pathway. Meanwhile, compound <strong>26</strong> was found to simultaneously inhibit FAK with DFG-out conformation and JAK3/Aurora B (IC₅₀ of 9.99 nM and 0.49 nM, respectively). <em>In vivo</em>, compound <strong>26</strong> effectively inhibited the tumorigenesis and metastasis of PDAC with desirable biosafety. Overall, these results suggested that compound <strong>26</strong> was a promising candidate for the treatment of PDAC.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"8 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, evaluation and mechanism study of novel pyrazole enamides to alleviate lung injury","authors":"Guoping Zhang, Mengjie Li, Yanghui Ou, Liya Ma, Jiayu Li, Kexin Sun, Tingting Xia, Jingbo Wang, Liyan Song, Yang Liu, Ran Lin, Hongliang Yao","doi":"10.1016/j.ejmech.2024.117068","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117068","url":null,"abstract":"Particulate matter with diameter ≤ 2.5 μm particles (PM2.5) can trigger pulmonary inflammation and lung injury. However, there is still no specific and effective treatment. Lansiumamide B (LB) is a natural <em>cis</em>-enamide compound isolated from wampee seeds, and has potential anti-inflammatory effect. Herein, two series of pyrazole enamide analogues were designed and synthesized based on the scaffold hopping strategy. The inhibition rates of inflammatory cytokines on compound <strong>11a</strong> were superior to other compounds and exhibited good dose-dependent manner and safety. Mechanism studies shown that <strong>11a</strong> activated the Keap1/Nrf2/HO-1 signaling pathway and promoted Nrf2 entering into nucleus. Further, <strong>11a</strong> alleviated pulmonary inflammation, collagen formation and promoted sputum secretion in PM2.5 induced lung injury mice. Besides, <strong>11a</strong> administration inhibited M1 macrophage polarization and neutrophil infiltration. Overall, <strong>11a</strong> is an effective anti-inflammatory agent which might be a potent candidate to treat lung injury.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"48 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the hydrophilic-lipophilic balance of free-base and Zn(II) tricationic pyridiniumporphyrins and irradiation wavelength in PDT against the melanoma cell lines","authors":"Martina Mušković, Martin Lončarić, Ivana Ratkaj, Nela Malatesti","doi":"10.1016/j.ejmech.2024.117063","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117063","url":null,"abstract":"The amphiphilic and asymmetric structure of porphyrins, when used as photosensitizers (PSs) for photodynamic therapy (PDT), has been shown through numerous previous studies to be a very important property that facilitates their entry into cells, which improves their efficiency in PDT. In this work, two groups of cationic AB₃ pyridiniumporphyrins, free-base and chelated with Zn(II), both substituted with alkyl chains of various lengths, were studied in PDT on melanoma cell lines. The aim was to investigate the impact of hydrophilic-lipophilic balance and Zn(II) chelation, and the importance of matching the irradiation wavelength to the optical properties of the PS on <em>in vitro</em> PDT efficiency. Therefore, spectroscopic studies, singlet oxygen production and lipophilicity as well as cellular uptake, localization and cytotoxicity studies of the two series of porphyrins were performed. In both series of porphyrins, the longest alkyl chain (17 C-atoms long) enables the greatest internalization of the PS. Chelation with Zn(II) resulted in better physicochemical properties, but slower cellular internalization. As expected, free-base porphyrins were more PDT efficient than their Zn(II) complexes after 30-minute photoactivation by low-fluence (2 mW/cm²) red light (643 nm). However the use of orange light (606 nm) with the same fluence rate was more suitable for Zn(II) porphyrins and resulted in similar overall toxicity to their free-base analogues with similar lipophilicity. Although the highest phototoxicity was achieved with the PSs carrying the longest alkyl chain, <strong>TMPyP3-C</strong>_{<strong>13</strong>}<strong>H</strong>_{<strong>27</strong>} and <strong>Zn(II)-TMPyP3-C</strong>_{<strong>13</strong>}<strong>H</strong>_{<strong>27</strong>} proved to be the most promising candidates for use in PDT as they exhibit high phototoxicity, but also greater selectivity towards melanoma cell lines (MeWo and A375) compared to fibroblasts (HDF).","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"29 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAT1 transporter as a target for breast cancer diagnosis and therapy","authors":"Z.Y. Zhou, T. Zhu, W.L. Zheng, Z.X. Zou, Q.F. Shan, Qing Chen, Gang Wang","doi":"10.1016/j.ejmech.2024.117064","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117064","url":null,"abstract":"Breast cancer is the main cause of female malignant tumor death in China. Numerous cellular molecules are associated with the onset and progression of breast cancer. However, these molecules have proven ineffective for the diagnosis and treatment of the disease, indicating a need for the identification of new biomarkers. LAT1 (SLC7A5) plays a crucial role in mediating the uptake of amino acids into breast cancer cells, influencing proliferation, invasion, migration, drug resistance, and prognosis through the mTOR signaling pathway. Notably, LAT1 exhibits differential expression across various types of breast cancer, positioning it as a promising candidate for diagnostic and therapeutic applications. Recent advancements in LAT1-targeting strategies for breast cancer have been made, particularly with the rapid developments in small molecular inhibitors and nanotechnology. In this article, we review the structure and function of LAT1, its relationship with breast cancer, and LAT1-mediated diagnostic and treatment strategies. This article specifically focuses on the LAT1-targeting strategy in breast tumors, aiming to evaluate its potential role as a novel biomarker for diagnosis and treatment.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"25 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Exploration of Isocitrate Dehydrogenase (IDH) Mutations: Tumorigenesis, Drug Discovery, and Covalent Inhibitor Advances","authors":"Conghao Gai, Hairong Zeng, Haoming Xu, Xiaoyun Chai, Yan Zou, Chunlin Zhuang, Guangbo Ge, Qingjie Zhao","doi":"10.1016/j.ejmech.2024.117041","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117041","url":null,"abstract":"Isocitrate dehydrogenase (IDH) is an enzyme that catalyses the oxidative decarboxylation of isocitrate, producing <em>α</em>-ketoglutarate (<em>α</em>-KG) relative to the hydroxylation of substrates. However, IDH mutants can further reduce <em>α</em>-KG to 2-hydroxyglutarate (2-HG) which competitively inhibits <em>α</em>-KG dependent enzymes, leading to the downregulation of normal hydroxylation pathways. Good IDH mutant inhibitors can effectively reduce the level of 2-HG and therefore disturb cellular malignant transformation. In this review, we introduce the biological functions of IDH, describe the tumorigenesis mechanisms of IDH variants, and review the structure-based drug discovery of clinical inhibitors during 2012-2024. We also find successful applications of covalent strategy in the development of irreversible IDH inhibitors. Biological screening methods are also collected in this paper, which may help researchers to rapidly construct workflows for drug discovery and development.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"7 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-GalCer sp2-Iminoglycolipid Analogs as CD1d-dependent iNKT Modulators: Evaluation of Their Immunotherapeutic Potential in Murine Models of Asthma and Autoimmune Hepatitis","authors":"Alan Chuan-Ying Lai, Manuel González-Cuesta, Chieh-Hsin Ho, Po-Yu Chi, Ko-Chien Wu, Gabriel Rocha, Juan C. Muñoz-García, Jesús Angulo, José M. García Fernández, Ya-Jen Chang, Carmen Ortiz Mellet","doi":"10.1016/j.ejmech.2024.117060","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117060","url":null,"abstract":"Invariant natural killer T (<em>i</em>NKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of <em>i</em>NKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical <em>i</em>NKT antigen, have shown improved preclinical results. However, significant obstacles remain, including the relatively laborious synthesis of α-glycosides and their vulnerability to degradation by α-glycosidases. To overcome these limitations, we explored the use of sp²-iminosugars, a class of glycomimetics, to replace the carbohydrate moiety in α-GalCer-like glycolipids. This substitution offers enhanced biostability and precise control over α-selectivity in glycosylation reactions. The resulting sp²-iminoglycolipids (sp²-IGLs) were tested for their immunomodulatory effects, demonstrating the ability to bind the α-GalCer binding site on the CD1d protein in antigen-presenting cells (APCs), and functioning as <em>i</em>NKT antagonists in α-GalCer-stimulated splenocytes. Notably, analogs featuring a 4-alkyl-1,2,3-aminotriazol-1-yl segment in place of the C₂₅ <em>N</em>-acyl tail in α-GalCer additionally exhibited mild agonistic activity in the absence of α-GalCer stimulation. Computational studies support the formation of stable CD1d– sp²-IGL and CD1d – sp²-IGL – T-cell receptor complexes, with significant differences in the dynamics depending on the glycone nature and lipid tail length. These findings provide a molecular rationale for the observed experimental data. Furthermore, <em>in vivo</em> studies using murine models of asthma and autoimmune hepatitis have identified promising sp²-IGL candidates for further development in immunotherapy.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"80 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer activity of salinomycin quaternary phosphonium salts","authors":"Marta Jędrzejczyk ,&nbsp;Michał Sulik ,&nbsp;Magdalena Mielczarek-Puta ,&nbsp;Gwan Yong Lim ,&nbsp;Małgorzata Podsiad ,&nbsp;Jakub Hoser ,&nbsp;Piotr Bednarczyk ,&nbsp;Marta Struga ,&nbsp;Adam Huczyński","doi":"10.1016/j.ejmech.2024.117055","DOIUrl":"10.1016/j.ejmech.2024.117055","url":null,"abstract":"<div><div>In recent years salinomycin has emerged as a promising anticancer drug. Many literature reports have proved its remarkable antiproliferative activity. Moreover, chemical modifications of salinomycin lead to analogues with even higher cytotoxicity against cancer cell lines and a better selectivity index for malignant cells than those of the unmodified compound or a standard anticancer drug such as doxorubicin. In this paper we report the synthesis of a series of twelve novel salinomycin conjugates and their characterization by spectroscopic and spectrometric methods. Salinomycin was conjugated with different triphenylphosphonium cations in order to find out whether the conjugation with mitochondrial targeting vectors would have a beneficial impact on biological properties. Salinomycin and its novel conjugates were tested to determine their <em>in vitro</em> antiproliferative and antimicrobial activity. Taking into account the presence of triphenylphosphonium moiety, the impact of the obtained analogues on mitochondria activity was evaluated by MitoTrackers dyes, furthermore their apoptosis effect and cell cycle arrest were assessed. In addition, the changes in the mitochondrial membrane potential were measured and the ability to generate reactive oxygen species was assessed. Finally, we conducted biophysical studies to investigate the impact of the obtained salinomycin analogues on mitochondrial respiration rates and their electrophysiological properties. Results of this study have proved that conjugation of salinomycin with phosphonium cations leads to promising results in the search for promising anticancer agents.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117055"},"PeriodicalIF":6.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel androgen-independent radiotracer with dual targeting of NTSR1 and PSMA for PET/CT imaging of prostate cancer","authors":"Qiong Wang, Zhongjing Li, Yong Huang, Chengze Li, Yiluo Li, Yi Peng, Zonghai Sheng, Ying Liang","doi":"10.1016/j.ejmech.2024.117050","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117050","url":null,"abstract":"A substantial proportion of patients with prostate cancer (PCa) develop treatment resistance or mortality after androgen deprivation therapy (ADT). Current methods for identifying and locating recurrent lesions using prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging, which relies on androgen levels, often result in diagnostic delays. Therefore, the development of an androgen-independent radiotracer is critical for the early identification of recurrent lesions. The neurotensin receptor 1 (NTSR1) is highly expressed in androgen-independent PCa lesions. Here, we synthesized a bispecific ligand targeting PSMA and NTSR1 by solid-phase peptide synthesis and formulated a ⁶⁸Ga-labelled bispecific radiotracer, ([⁶⁸Ga]Ga-NT-PSMA). This radiotracer exhibited a high radiochemical yield (71.27% ± 1.58%) and demonstrated an affinity for NTSR1 (39.32 ± 2.98 nM) and PSMA (63.47 ± 5.14 nM) <em>in vitro</em>. Small animal PET imaging showed comparable uptake of [⁶⁸Ga]Ga-NT-PSMA and the monomeric radiotracer [⁶⁸Ga]Ga-DOTA-NT20.3 in mice bearing androgen-independent PC3 (3.64 ± 0.49 %ID/g vs. 5.60 ± 1.42 %ID/g, nonsignificant [ns]) and DU145 tumors (2.49 ± 0.20 %ID/g vs. 2.34 ± 0.18 %ID/g, ns) at 90 min post-injection. In androgen-dependent 22Rv1 xenografts, [⁶⁸Ga]Ga-NT-PSMA uptake was lower (1.94 ± 0.29 %ID/g) than [⁶⁸Ga]Ga-PSMA-11 (3.94 ± 0.26 %ID/g, <em>P</em> &lt; 0.001). Nevertheless, [⁶⁸Ga]Ga-NT-PSMA effectively imaged all three xenograft types with high contrast, an achievement not possible with monomeric radiotracers alone. These results indicate that imaging with [⁶⁸Ga]Ga-NT-PSMA is independent of the androgen dependence of the model, highlighting its potential as a promising nuclear medicine diagnostic tool for the early identification and localization of castration-resistant PCa lesions.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"3 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and biological evaluation of novel pleuromutilin derivatives with methicillin-resistant Staphylococcus aureus -targeting phenol linker groups","authors":"Yunpeng Yi ,&nbsp;Jiaming Zhang ,&nbsp;Shuqian Lin ,&nbsp;Haiting Wang ,&nbsp;Guiyu Li ,&nbsp;Shifa Yang ,&nbsp;Ruofeng Shang ,&nbsp;Rongling Zhang ,&nbsp;Fei Li","doi":"10.1016/j.ejmech.2024.117061","DOIUrl":"10.1016/j.ejmech.2024.117061","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) remains a significant global health threat, necessitating the development of new therapeutic agents. Pleuromutilin derivatives offer a promising solution due to their potent antibacterial activity, particularly against Gram-positive bacteria such as MRSA. In this study, we synthesized a series of pleuromutilin derivatives with phenol linker containing C14 side chains and evaluated <em>in vitro</em> and <em>in vivo</em> antibacterial activities. Several compounds showed potent activity against MRSA and <em>Staphylococcus aureus</em> with minimal inhibitory concentrations (MICs) as low as 0.03125 μg/mL. In particular, compounds <strong>a4</strong> and <strong>b4</strong> showed rapid bactericidal activity, significantly reducing MRSA loads in time-kill kinetics and exhibiting slower resistance development compared to tiamulin. <em>In vivo</em>, compound <strong>a4</strong> showed superior efficacy in reducing MRSA-induced lung damage in a mouse model at a lower effective dose (ED50 = 6.48 mg/kg) compared to tiamulin (ED50 = 11.38 mg/kg). Molecular docking and molecular dynamics studies also showed that compound <strong>a4</strong> binds strongly to the ribosomal peptidyl transferase center (PTC), a key target for pleuromutilin derivatives. These results suggest that compound <strong>a4</strong>, with its enhanced antibacterial activity and low resistance potential, is a promising candidate for further development as an effective treatment for MRSA infections.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117061"},"PeriodicalIF":6.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and evaluation of a novel BODIPY fluorescent probe targeting integrin αvβ3 for cancer diagnosis","authors":"Bin Rong,&nbsp;Xiaochun Dong,&nbsp;Weili Zhao","doi":"10.1016/j.ejmech.2024.117056","DOIUrl":"10.1016/j.ejmech.2024.117056","url":null,"abstract":"<div><div>A series of integrin α_vβ₃ targeting BODIPY-RGD conjugate were designed and synthesized. Their <em>in vitro</em> and <em>in vivo</em> fluorescence imaging behaviors were investigated. The small molecule compound was designed as an optical imaging near-infrared fluorescent dye which was combined RGD peptide with the <em>meso</em>-amide BODIPYs using succinic moiety as a spacer. The construction alleviated the traditional BODIPY problems including poor water solubility, aggregate caused quench (ACQ) effect, low biocompatibility, etc. In cellular research, <strong>BDP-RGD-2</strong> showed rapid, selective uptake in 3 highly expressing integrin α_vβ₃ cell lines MDA-MB-231, A549, U87MG at different extent rather than an integrin α_vβ₃ low level expression cell MCF-7. In animal study, fluorescence imaging of U87MG model targeted by <strong>BDP-RGD-2</strong> displayed a highest tumor uptake level and T/N ratio up to 6 h after tail-intravenous injection, which demonstrated <strong>BDP-RGD-2</strong> was a promising probe for tracing integrin α_vβ₃ overexpressing tumors.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"282 ","pages":"Article 117056"},"PeriodicalIF":6.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601756","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}