Bioorganic Chemistry最新文献

{"title":"Hydroxychavicol derivatives from Piper betle Linn. as natural PDE4 inhibitors with anti-inflammatory effects","authors":"Jiazhi Ou ,&nbsp;Fang Zhong ,&nbsp;Peiluo Huang,&nbsp;Yan Zhang,&nbsp;Shenghong Xie,&nbsp;Peng Wu,&nbsp;Junyi Li,&nbsp;Haihang Qiu,&nbsp;Chunying Wang,&nbsp;Yiyou Huang,&nbsp;Qian Zhou,&nbsp;Zhongbin Cheng,&nbsp;Hai-Bin Luo","doi":"10.1016/j.bioorg.2025.108294","DOIUrl":"10.1016/j.bioorg.2025.108294","url":null,"abstract":"<div><div>PDE4 inhibitors have been developed as anti-inflammatory medications primarily used in the clinical treatment of pulmonary inflammations such as asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. However, the application of these drugs is usually restricted by obvious side effects, such as nausea and vomiting. Our previous study found that several natural PDE4 inhibitors or their modified derivatives showed minimal side effects, particularly reduced incidence of nausea and vomiting, which aroused our interest in searching for natural PDE4 inhibitors. In this study, a chemical investigation of an active fraction of <em>Piper betle</em> L. leaves led to the characterization of 23 hydroxychavicol derivatives, including 18 hydroxychavicol-type lignans. Compounds <strong>1</strong>–<strong>9</strong> were new lignans, with three of them being racemates that were eventually resolved into isolated (+)- and (−)-enantiomers. Compounds <strong>1–5</strong> and <strong>10</strong>, neolignans characterized by a dioxane moiety, were unique to this species within the genus <em>Piper</em>. Compounds <strong>5</strong> and <strong>10</strong> were the sole sesquineolignans found in the genus <em>Piper</em>. Compounds <strong>5</strong>, <strong>7</strong>–<strong>14</strong>, <strong>16</strong>, <strong>17</strong>, and <strong>21</strong> exhibited considerable inhibition towards PDE4 with IC₅₀ values ranging from 1.8 to 10 μM, with hit <strong>7</strong> exhibiting remarkable activity (1.8 μM). Further anti-inflammatory assays revealed that compounds <strong>5</strong>, <strong>7</strong>, <strong>9</strong>, and <strong>16</strong> decreased the expression of several key inflammatory mediators in LPS-stimulated RAW 264.7 cells. Notably, <strong>16</strong> was comparable to the positive control rolipram at the same concentration of 10 μM. A primary study of the mechanism of action revealed that <strong>16</strong> may exert anti-inflammatory effect by inhibiting the NF-κB signaling pathway, displaying significant inhibition of the phosphorylation of IκB-α and p65 at concentrations of 5 and 10 μM. These findings suggest that hydroxychavicol derivatives from <em>P. betle</em> L. leaves may serve as new PDE4 inhibitors, offering promising leads for the development of anti-inflammatory medications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108294"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478806","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":"Recent advances in transition metal-mediated/ catalyzed radiofluorination of arenes and heteroarenes for positron emission tomography","authors":"Haiyan Chen ,&nbsp;Buchuan Zhang ,&nbsp;Siyu Chen ,&nbsp;Feng Xiong ,&nbsp;Xiaohua Zhu ,&nbsp;Bo Yu ,&nbsp;Sihui Long","doi":"10.1016/j.bioorg.2025.108272","DOIUrl":"10.1016/j.bioorg.2025.108272","url":null,"abstract":"<div><div>Positron emission tomography (PET) imaging endows the possibility of precise diagnosis and effective treatment of diseases. Aromatic (hetero)cycle is one of the most fundamental groups in pharmaceuticals as well as in the development of PET tracers. In particular, incorporation of ¹⁸F to aromatic (hetero)cycles has accelerated the progress of nuclear medicine tracers. Current trend indicates a rapid progress in ¹⁸F-labeling of aromatic (hetero)cycles for PET imaging. Transition metal-catalyzed ¹⁸F-labeling method speeds up the reaction by lowering the activation energy of the substrate by the metal complex. The reaction conditions are mild, and a wide range of substrates can be used. In this article we systematically reviewed the methods of radioactive ¹⁸F-labeling of aromatic (hetero)cycles with different precursors mediated by transition metals‑copper, ruthenium, nickel, palladium, silver, and titanium. The precursors, radiolabeling conditions, catalytic efficiency, catalytic mechanism, optimization of transition metal-catalyzed ¹⁸F-labeling methods, and corresponding frontier applications of ¹⁸F-labeled molecular probes were discussed.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108272"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488237","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":"Characterization and application in recombinant N-GlcNAc-protein production of a novel endo-β-N-acetylglucosaminidase from Listeria booriae","authors":"Weian Mao ,&nbsp;Yongheng Rong ,&nbsp;Hongmei Zhang ,&nbsp;Fang Yuan ,&nbsp;Yankang Wang ,&nbsp;Mei Wang ,&nbsp;Linhan Wang ,&nbsp;Peng George Wang ,&nbsp;Min Chen ,&nbsp;Shengjun Wang ,&nbsp;Yun Kong","doi":"10.1016/j.bioorg.2025.108290","DOIUrl":"10.1016/j.bioorg.2025.108290","url":null,"abstract":"<div><div>Endo-β-<em>N</em>-acetylglucosaminidases (ENGases) are essential enzymes for hydrolyzing <em>N</em>-glycans, with applications in protein <em>N</em>-glycosylation analysis and glycoprotein synthesis. In this study, a novel GH18 family ENGase, Endo-LB, was identified from <em>Listeria booriae</em> FSL A5–0281. Composed of 593 amino acids (65.78 kDa), Endo-LB features with two domains: an Endo S-like catalytic domain and a mucin-binding protein (MucBP) domain. Recombinant Endo-LB, expressed in <em>Escherichia coli</em> BL21 (DE3) pLysS, exhibited a specific activity of 198.25 U/mg and hydrolyzed high mannose-type <em>N</em>-glycans at a temperature from 4 °C to 60 °C with optimal activity at 37 °C and pH 6.0 (range 3.0 to 10.0), making it versatile for various environmental conditions. The MucBP domain does not affect soluble Endo-LB activity but influences interaction with mucin on cell surface, suggesting potential application in targeting specific glycoproteins in complex biological environments. To address the heterogeneity of <em>N</em>-glycans in <em>Pichia pastoris</em> (<em>Komagataella phaffii</em>) expression, Endo-LB was further expressed in the Golgi of <em>P. pastoris</em>, efficiently producing glycoproteins, such as Erythropoietin (EPO) (37 mg/L) and Darbepoetin α (53 mg/L) with nearly complete <em>N</em>-glycans truncation, which can be further extended to generate diverse <em>N</em>-glycan structures. These findings highlight the versatility and potential utility of Endo-LB in glycoprotein engineering and biotechnological applications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108290"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453212","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":"Targeted discovery of diterpene compounds ostamycins with anti-influenza a viral activity from a deepsea-derived Streptomyces strain","authors":"Lukuan Hou ,&nbsp;Shuyao Wang ,&nbsp;Yuanhang Zhang ,&nbsp;Xue Yang ,&nbsp;Zihui Chen ,&nbsp;Yuxuan Gao ,&nbsp;Wenli Li","doi":"10.1016/j.bioorg.2025.108268","DOIUrl":"10.1016/j.bioorg.2025.108268","url":null,"abstract":"<div><div>Heterologous expression of a nonconventional terpene biosynthetic gene cluster from the deepsea-derived <em>Streptomyces amphotericinicus</em> DS22–01 led to the production of a novel cyclic diterpene, ostamycin A (<strong>1</strong>). Anti-influenza A virus activity evaluation revealed that compound <strong>1</strong> showed significant activity with an IC₅₀ value of 4.72 μM, which was much stronger than that of the positive control ribavirin (IC₅₀ = 20.80 μM). Inspired by its intriguing activity, yield optimization was achieved through a combined approach involving promoter engineering and codon modification in a stepwise manner. This strategy led to a ∼ 13-fold increase in the production of ostamycin A (<strong>1</strong>), as well as the concurrent accumulation of another novel cyclic diterpene, ostamycin B (<strong>2</strong>), which also displayed anti-influenza A virus activity with an IC₅₀ value of 195.59 μM. The planar structures and stereochemistry of compounds <strong>1</strong> and <strong>2</strong> were established through extensive MS and NMR spectroscopic analyses together with ECD calculations. Further investigations revealed that compound <strong>1</strong> inhibits the influenza A virus (A/Puerto Rico/8/34) replication by directly targeting the nucleoprotein (NP). These findings highlight compound <strong>1</strong> as a promising lead for the development of novel influenza virus inhibitors.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108268"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453215","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":"Novel bis-pocket binding aldose reductase inhibitors sensitize MCF-7/ADR cells to doxorubicin in a dual-role manner","authors":"Chao Zhang ,&nbsp;Shuling Peng ,&nbsp;Ziyou Zheng ,&nbsp;Zhenqiang Chen ,&nbsp;Mingyue Li ,&nbsp;Nengneng Huang ,&nbsp;Zhijun Liu ,&nbsp;Mao-Xun Yang ,&nbsp;Heru Chen","doi":"10.1016/j.bioorg.2025.108286","DOIUrl":"10.1016/j.bioorg.2025.108286","url":null,"abstract":"<div><div>Multidrug resistance (MDR) represents a bottleneck in the treatment of breast cancer. Although the potential of aldose reductase inhibitors (ARIs) as sensitizers against MDR has been explored in recent decades, the intrinsic mechanism still needs to be elucidated, and promising agents in the clinic need to be developed. In this study, three novel ARIs (<strong>5a-c</strong>), characterized by bis-pocket binding, were designed and synthesized. Inhibitory activity is positively correlated with antioxidation and benefits from rigid spacers. Only <strong>5a</strong> with less activities in inhibition and antioxidation was demonstrated as a stronger sensitizer against doxorubicin (DOX)-resistant MCF-7 cells (MCF-7/ADR) than epalrestat (EPA). Either <strong>5a</strong> or EPA may decrease GSH abundance and increase ROS, Fe²⁺, and lipid peroxidation levels. The restorative effects of both ARIs may be blocked by <em>N</em>-acetyl cysteine (NAC). These data suggest that both <strong>5a</strong> and EPA may restore the sensitivity of MCF-7/ADR cells to DOX by increasing ferroptosis activity. Furthermore, the inhibition of AKR1B1 by <strong>5a</strong>, as well as by EPA, dramatically decreased both <em>p</em>-STAT3 and SLC7A11 expression. Gene knockdown of AKR1B1 has the same effects as AKR1B1 inhibition. This evidence indicates that both ARIs can suppress MCF-7/ADR cell growth via the upregulation of ferroptosis activity via the AKR1B1/STAT3/SLC7A11 axis. Additionally, <strong>5a</strong> was found to increase the accumulation of intramolecular DOX by inhibiting ABCB1, but EPA did not. These results support that <strong>5a</strong> is a promising sensitizing agent against multidrug resistance in breast cancer.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108286"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453211","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":"Exploring the larvicidal and pupicidal activities of new functionalized pyridines against Culex pipiens L. referring to molecular docking and SAR studies","authors":"Safaa I. Elewa ,&nbsp;Doaa R. Abdel-Haleem ,&nbsp;Ahmed H. Tantawy ,&nbsp;Hany I. Mohamed ,&nbsp;Walaa H. Lashin","doi":"10.1016/j.bioorg.2025.108283","DOIUrl":"10.1016/j.bioorg.2025.108283","url":null,"abstract":"<div><div>Pesticides are intensively employed to manage pests, but they pose a great challenge, developing pesticide resistance. So, searching for novel chemical structures is crucial to overcoming insecticide resistance. Herein, a new functionalized pyridine derivative <strong>4</strong> was effectively constructed in a one-step reaction through reacting four components, including piperonal, ethyl cyanoacetate, 2-acetylthiophene, and ammonium acetate, under ultrasonic conditions. Treatment of the derivative <strong>5</strong> with hydrazine hydrate in ethanol afforded the acetohydrazide derivative <strong>8</strong> that was utilized as a key precursor for the synthesis of Schiff^'s bases and other nicotinonitriles. Moreover, new acetohydrazone derivatives <strong>(19–21)</strong> were furnished by the reaction of <strong>8</strong> with isatin, <em>n</em>-vinylpyrrolididone, and galactose, respectively. The data obtained from the spectral measurements was the basis for elucidating the structures of the new derivatives. The larvicidal and pupicidal potencies of the synthesized thienyl pyridine derivatives were assessed against <em>Culex pipiens</em> L., and most exhibited moderate to good activity. The larvae were more susceptible to <strong>17</strong>, <strong>19</strong>, <strong>6</strong> and <strong>13</strong> with LC₅₀ of 1.57, 1.91, 2.36 and 2.90 ppm, respectively, while pupae were less susceptible with LC₅₀ of 4.17, 5.03, 6.16 and 7.45 ppm, respectively. The various functional groups connected to the pyridine ring led to variations in the toxicity of synthesized compounds, which were clarified through the SAR study. At the same time, a molecular docking study was performed to demonstrate the compound's mode of action and the effect of inserted moieties on binding with the nicotinic acetylcholine receptors (<em>n</em>AChRs). Collectively, the results imply that the thienyl pyridine derivatives could be used as mosquitocidal agents against <em>C. pipiens</em> larvae and pupae.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108283"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437046","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":"Punicalagin as an Artemis inhibitor synergizes with photodynamic therapy in tumor suppression","authors":"Xuening Chen ,&nbsp;Changkun Chen ,&nbsp;Zuoan Li ,&nbsp;Chun Liu ,&nbsp;Zhonghui Lin","doi":"10.1016/j.bioorg.2025.108282","DOIUrl":"10.1016/j.bioorg.2025.108282","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is a minimally invasive treatment that utilizes a photosensitizer, specific light wavelengths, and oxygen to generate reactive oxygen species (ROS), causing oxidative damage and tumor cell death. However, the effectiveness of PDT can be reduced by the intrinsic antioxidant and DNA repair mechanisms of tumor cells. Artemis (SNM1C/DCLRE1C) is an endonuclease essential for repairing DNA double-strand breaks (DSBs) <em>via</em> non-homologous end-joining (NHEJ). Herein, we conducted a high-throughput small-molecule screening and identified Punicalagin (PUG), a natural polyphenol from pomegranate, as a novel Artemis inhibitor with an IC₅₀ value of 296.1 nM. We also investigated the effects of PUG combined with PDT in tumor treatment, using the pentalysine β‐carbonylphthalocyanine zinc (ZnPc5K) as the photosensitizer. In HeLa cells, ZnPc5K-based PDT induced significant DSBs, which could be repaired by the intrinsic DNA repair mechanisms within 12 h. Co-treatment with PUG compromised DNA repair, promoted cell apoptosis, inhibited cell invasion, and suppressed the growth of various tumor cells. Furthermore, in a mouse xenograft model, the combination of PUG and ZnPc5K-PDT effectively inhibited tumor growth with minimal side effects. These findings suggest that PUG, as an Artemis inhibitor, can enhance the therapeutic efficacy of PDT in tumor suppression by impairing DNA repair through the NHEJ pathway.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108282"},"PeriodicalIF":4.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437042","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 molecular modeling of new Pyrazolyl-Benzimidazolone hybrids targeting breast Cancer","authors":"Mohamed Adardour ,&nbsp;Al-Hassan M. Mustafa ,&nbsp;Mehdi Oubahmane ,&nbsp;Marouane Ait Lahcen ,&nbsp;Emad M. Seif ,&nbsp;Manal Abdel Fattah Ezzat ,&nbsp;Elena Zaballos-García ,&nbsp;Joel T. Mague ,&nbsp;Ismail Hdoufane ,&nbsp;Driss Cherqaoui ,&nbsp;Oliver H. Krämer ,&nbsp;Wolfgang Sippl ,&nbsp;Hany S. Ibrahim ,&nbsp;Abdesselam Baouid","doi":"10.1016/j.bioorg.2025.108269","DOIUrl":"10.1016/j.bioorg.2025.108269","url":null,"abstract":"<div><div>Methyl-piperidino-pyrazole (MPP) is a pyrazole derivative acting as a lead estrogen receptor (ER) antagonist and has an anti-breast cancer effect. Since some benzimidazole derivatives were reported for their inhibitory activity against breast cancer, hybrids from these reported compounds (<strong>5a-c</strong>, <strong>6a-c</strong>, <strong>7a-c</strong> and <strong>8a-c</strong>) were designed to develop anti-breast cancer agents. The synthesis involved 1,3-dipolar cycloaddition of nitrilimines on the benzimidazolone derivatives <strong>2a-b</strong> and <strong>3a-b</strong> which occurred with chemo- and regioselectivity depending on the dipole and was confirmed by an X-ray structure of <strong>6b</strong>. <em>In vitro</em> biological testing of the newly prepared compounds against the 60-cell line panel showed that <strong>5a-c</strong> and <strong>6a-c</strong> with a partially unsaturated pyrazole ring possessed a high GI% in the T-47D breast cancer cell line with a selectivity margin against different cell lines. Five compounds were selected for apoptotic studies in T-47D cells, of which <strong>6a</strong> arrested cells in G1 phase and caused more apoptosis than MPP. The MTT assay revealed that compound <strong>6a</strong> has an IC₅₀ = 6.77 ± 0.03 μM against T-47D cells. Furthermore, <strong>6a</strong> reduced the estrogen receptor 1 gene expression levels 3-fold in T-47D cells. Molecular dynamics simulations indicated that the complex of the active compound <strong>6a</strong> remained stable over the last 150 ns. An analysis of the binding mode revealed that compound <strong>6a</strong> exhibited a similar conformation compared to MPP and the co-ligand in the active site of <em>via</em> a specific pose involving noncovalent interactions.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108269"},"PeriodicalIF":4.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437097","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":"Construction of a smart dual-responsive targeted drug nanocarrier for imaging and treatment of breast cancer cells","authors":"Hongyu Qian ,&nbsp;Sanxia Wang ,&nbsp;Xin Chen ,&nbsp;Ninghan Feng ,&nbsp;Yuting Zhang ,&nbsp;Xiaoli Wang ,&nbsp;Nandi Zhou","doi":"10.1016/j.bioorg.2025.108284","DOIUrl":"10.1016/j.bioorg.2025.108284","url":null,"abstract":"<div><div>Breast cancer has become one of the most common cancers worldwide, but the effectiveness of the conventional drug chemotherapy is still restricted. Therefore, precision imaging and targeted therapy against breast cancer cells have become a hot research topic. In this study, a dual-responsive nanocarrier system based on multi-functionalized gold nanoparticles (GNP) was developed for simultaneous diagnosis and treatment of breast cancer cells. The nanoparticles were modified with an aptamer which specifically recognizes MUC-1 protein on the surface of the breast cancer cell MCF-7, achieving precise cellular targeting. Upon entry into the cell, the decrease of pH in the intracellular environment causes the detachment of the i-motif sequence from GNP. Cy5 labeled at the end of i-motif, which is previously quenched by GNP thus restores its fluorescence, achieving the imaging of the cancer cells. Additionally, chemotherapeutic drug gemcitabine (GEM) is covalently attached to GNP through a rationally designed oligopeptide linker CGFLG. Cathepsin B, which is overexpressed in MCF-7 cells, can precisely cleave the CGFLG linker and release GEM to the cells, thereby achieving the targeted drug delivery and treatment. When 4 nM nanocarrier was applied, the inhibition rate of MCF-7 cells was approximately 70 %. This dual-responsive nanocarrier system integrates the targeting, imaging and therapeutic functions in a simple GNP platform. The high targeting efficiency of the nanocarrier reduces the non-specific binding and toxic effects on normal cells, while enhances the toxicity toward cancer cells. Therefore, it may have great prospects in medical applications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108284"},"PeriodicalIF":4.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445245","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":"Isatin-modified Calixarene derivatives: A comprehensive study on synthesis, enzyme inhibition, antioxidant, antimicrobial, and Antiproliferative activities","authors":"Alev Oguz ,&nbsp;Ahmet Uysal ,&nbsp;Begum Nurpelin Saglik Özkan ,&nbsp;Mehmet Oguz ,&nbsp;Mustafa Yilmaz","doi":"10.1016/j.bioorg.2025.108280","DOIUrl":"10.1016/j.bioorg.2025.108280","url":null,"abstract":"<div><div>In this article, a series of calix[4]arenes derivatized with isatin derivatives at the phenolic-O position were synthesized as potential theranostic molecules for antitumor therapy. The cytotoxic mechanism of action of the synthesized compounds was determined by Alamar Blue assay and flow cytometry using MCF-7, MDA-MB-231, DLD1, HeLa and A549 human cancer cell lines and their ability to penetrate into PNT1A healthy epithelial cells. To detect DNA damage, the Comet test was applied after the synthesized compounds interacted with the cells. As a result, it was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. Within the scope of enzyme inhibition experiments, studies were carried out on aromatase and COX-2 enzymes and it was determined that the compounds in the series showed inhibitory activity at varying rates. Especially compounds <strong>CLX-A3</strong>, <strong>CLX-A4</strong>, <strong>CLX-B3</strong> and <strong>CLX-B5</strong> attract attention with their enzyme inhibitor potential. Also, the antioxidant activities of the compounds whose synthesis was completed were also investigated and it was observed that the examined derivatives also had antioxidant activity potential.</div><div>As a result of the antibacterial and antifungal test performed with broth microdilution, it was observed that the compounds had significant antibacterial and antifungal activity. The lowest MIC values were recorded as 0.006 mg/ml against Sarcina lutea and 0.048 against <em>Candida albicans</em>. In addition, the compound CLX-B3was observed to be effective against all strains including, <em>Klebsiella pneumoniae</em> and <em>Salmonella enteritidis</em> (Gram-negative pathogenic bacteria).</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108280"},"PeriodicalIF":4.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437044","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}