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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2021 · IF 4.098

The pH and mercury ion stimuli-responsive supramolecular assemblies of cucurbit[7]uril and Hoechst 33342

Qin Wang,Li-Bing Lü,Zhu Tao,Tao Sun,Qing Tang,Ying Huang

In the present work, we have investigated the effect of pH and mercury ions on the host–guest complex formed between cucurbit[7]uril (Q[7]) and Hoechst 33342 (H33342). 1 H NMR, UV–vis and fluorescence spectroscopy revealed that acid/base stimulation could change the binding stoichiometry between Q[7] and H33342. The results suggest that two complexation equilibria (1:1 and 2:1) may exist between H33342 and Q[7] at pH 2.0 and 4.5, respectively. However, a 1:1 host–guest complex was formed between H33342 and Q[7] at pH 7.0 and 10.0. Q[7] shows differential affinities for the protonated and neutral forms of H33342 dye. Moreover, the switching between H33342∙2H + @2Q[7](1:2) at pH 4.5 and H33342∙H + @Q[7](1:1) at pH 7.0 was reversible. Furthermore, as a metal stimulus, Hg 2+ ions could push (i) Q[7] from the piperazine ring to the benzimidazole position with a 1:1 guest–host ratio and (ii) a second Q[7] onto the ethyl position with a 1:2 guest–host stoichiometry. This stimulus response system will have potential applications in the field of molecular switch design.

研究领域: 超分子化学 · 分析化学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF MEDICINAL CHEMISTRY · 2018 · IF 6.253

Novel Pyrrole–Imidazole Polyamide Hoechst Conjugate Suppresses Epstein–Barr Virus Replication and Virus-Positive Tumor Growth

Zhehong Cheng,Wei Wang,Chunlei Wu,Xiaohua Zou,Lijing Fang,Wu Su,Pu Wang

Epstein–Barr virus (EBV) establishes latent infection and is associated with several types of lymphomas and carcinomas. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV-positive tumor cells. EBNA1 binds to the origin of virus plasmid replication (OriP) on the EBV episome to initiate virus DNA replication and regulates virus gene expression as a transcriptional activator. In this study, we designed and synthesized a pyrrole–imidazole polyamide–Hoechst 33258 conjugate named EIP-2 (2), which specifically binds to the OriP region with high affinity, to interrupt EBNA1-OriP binding in vitro and in vivo. By eradicating the EBV episome in EBV-positive cells, compound 2 selectively inhibited EBV-positive cell proliferation. Moreover, the injection of 2 significantly suppressed tumor growth in the mice xenograft tumor model. These findings demonstrate that compound 2 is a potential therapeutic candidate for the treatment of EBV-associated tumors.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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INORGANIC CHEMISTRY COMMUNICATIONS · 2019 · IF 1.795

Host–guest assembly of H33258 dye in cucurbit[7]uril and specific recognition for HPO42− anion

Mei-Xiang Yang,Ming Liu,Mei Yang,Qin Wang,Xi Zeng,Zhu Tao,Xin Xiao,Ying Huang

In the present work, a well-known host–guest inclusion complex comprising a cucurbit[7]uril (Q[7]) and an important biological dye, Hoechst-33258 (H33258) was selected as a fluorescence probe. In contrast to the pH conditions in which H33258 is exhibited in the literature, these being, mono- or di-protonated states, in the present work, we selected an extreme case, whereby H33258 was displayed in an anionic state (pH = 11). The investigation of the host–guest interaction demonstrated similar inclusion modes in a wide pH range, that is the dumbbell-like inclusion complex in which one Q[7] includes piperazine moiety and another Q[7] includes the phenol moiety of H33258. Moreover, investigation on the binding capacity of the 15 selected anions under three representative pH levels (pH = 2, pH = 4.5 and pH = 11, respectively) indicated that the H33258@Q[7] probe displayed unique selectivity on HPO 4 2 − anion in medium at pH = 11. More importantly, the probe could open a new platform in Q[ n ]-chemistry, that is the Q[ n ]-based host–guest interaction systems can apply in anion recognition or response.

CAS / MDL: 1643-19-2
研究领域: 化学 · 生物化学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2023 · IF 3.4

pH-responsive resveratrol-loaded ZIF-8 nanoparticles modified with tannic acid for promoting colon cancer cell apoptosis

Xueqiang Sun,Fuxin Li,Lingyan Yuan,Zhitong Bing,Xun Li,Kehu Yang

Resveratrol (Res) is known for its potential in treating various types of cancers, with a particular advantage of causing minimal toxic side effects. However, its clinical application is constrained by challenges such as poor bioavailability, low water solubility, and chemical instability in neutral and alkaline environments. In light of these limitations, we have developed a pH-responsive drug delivery nanoplatform, Res@ZIF-8/TA NPs, which exhibits good biocompatibility and shows promise for in vitro cancer therapy. Benefiting from the mild reaction conditions provided by zeolitic imidazolate frameworks (ZIFs), a “one-pot method” was used for drug synthesis and loading, resulting in a satisfactory loading capacity. Notably, Res@ZIF-8/TA NPs respond to acidic environments, leading to an improved drug release profile with a controlled release effect. Our cell-based experiments indicated that tannic acid (TA) modification enhances the biocompatibility of ZIFs. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT assay), Hoechst 33342/PI staining, cell scratch assay, Transwell and Reverse Transcription quantitative PCR (RT-qPCR) assays further demonstrated that Res@ZIF-8/TA NPs inhibited colon cancer cell migration and invasion, and promoted apoptosis of colon cancer cells, suggesting a therapeutic potential and demonstrating anti-cancer properties. In conclusion, the Res@ZIF-8/TA NPs pH-responsive drug delivery systems we developed may offer a promising avenue for cancer therapy. By addressing some of the challenges associated with Res-based treatments, this system could contribute to advancements in cancer therapeutics.

CAS / MDL: 10102-40-6
研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer

Dong-mei Li,Fu-cui Zhu,Jie Wei,Jia-xiu Xie,Jun-hui He,Dong-mei Wei,Yi Li,Ke-dao Lai,Li-min Liu,Qi-biao Su,Gui-ning Wei,Bin Wang,Yan-cheng Liu

Ethnopharmacological relevance Polyrhachis vicina Roger ( P. vicina ), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis , hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia . Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. Aim of the study The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. Methods To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology , molecular docking, qRT-PCR, western blotting , CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. Results Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. Conclusion According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

CAS / MDL: 51-21-8
研究领域: 药理学 · 肿瘤学 · 传统中药 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

User-Friendly Multifunctional Red-Emissive Carbon Dots for Rapid Cell Nucleus Staining via Targeting Nuclear Proteins

Jingbo Sun,Hongchen Li,Min Ouyang,Jing Cheng,Dong Xu,Xiaofeng Tan,Qinlu Lin

Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.

研究领域: 细胞生物学 · 疾病诊断 · 材料科学 · 光学性质 · 生物医学应用
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF FLUORESCENCE · 2017 ·Vol. 27 ·期 5 ·1815-1828 · IF 1.461

Groove Binding of Vanillin and Ethyl Vanillin to Calf Thymus DNA

Xia Kaixin,Zhang Guowen,Li Song,Gong Deming

Vanillin (VAN) and ethyl vanillin (EVA) are widely used food additives as flavor enhancers, but may have a potential security risk. In this study, the properties of binding of VAN or EVA with calf thymus DNA (ctDNA) were characterized by multi-spectroscopic methods, multivariate curve resolution-alternating least-squares (MCR–ALS) algorithm and molecular simulation. The concentration profiles for the components (VAN or EVA, ctDNA and VAN–ctDNA or EVA–ctDNA complex) by the MCR–ALS analysis showed that VAN or EVA interacted with ctDNA and formed VAN–ctDNA or EVA–ctDNA complex. The groove binding of VAN or EVA to ctDNA was supported by the results from viscosity measurements, melting studies, denaturation experiments, and competitive binding investigations. Analysis of the Fourier transform infrared spectra corroborated the prediction by molecular docking that VAN and EVA preferentially bound to thymine bases region of ctDNA. The circular dichroism and DNA cleavage assays indicated that both VAN and EVA induced conformational change (from B − like DNA structure toward to A − like form), but didn’t lead to a significant damage on DNA. The fluorescence quenching of Hoechst 33,258–ctDNA complex by VAN or EVA was a static quenching, and hydrogen bonding and van der Waals forces were main forces. This study has provided insights into the mechanism of interaction between VAN or EVA with ctDNA, and may also help better understand their potential toxicity with regard to food safety. VAN or EVA binds to A–T rich regions of ctDNA in the minor groove.

CAS / MDL: 3546-41-6
研究领域: 化学 · 生物化学 · 分子生物学 · 食品科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2012 · IF 7.404

Hyperbranched cationic amylopectin derivatives for gene delivery

Yanfang Zhou,Bin Yang,Xianyue Ren,Zhenzhen Liu,Zheng Deng,Luming Chen,Yubin Deng,Li-Ming Zhang,Liqun Yang

A series of hyperbranched cationic amylopectin derivatives conjugated with 1,2-ethylenediamine, diethylenetriamine and 3-(dimethylamino)-1-propylamine residues, named as EDA-Amp, DETA-Amp and DMAPA-Amp, were synthesized by the N,N’- carbonyldiimidazole activation method at room temperature. Their structures were characterized by FTIR and 1 H NMR analyses, and their buffering capability was assessed by acid-base titration. The amylopectin derivatives exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI) in the hemolysis and MTT assays . Atomic force microscopy and optical microscopy confirmed that the amylopectin derivatives exhibited lower damage for erythrocytes than bPEI. The amylopectin derivatives could bind and condense plasmid DNA (pDNA) to form the complexes with the size ranging from 100 to 300 nm. The resultant complexes showed higher transfection efficiency in 293T cells than in A549 cells. The DMAPA-Amp derivative-mediated gene transfection for Forkhead box O1 exhibited higher protein expression than that of the EDA-Amp and DETA-Amp derivatives in 293T cells, which was analyzed by western blot , flow cytometry and Hoechst staining assay. On the basis of these data, amylopectin derivatives exhibit potential as nonviral gene vectors .

研究领域: 药学 · 分子生物学 · 生物技术 · 基因治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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