- Reduction of 4-azidonaphthalimide with different phosphine ligands and exploration of their spectroscopic properties
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A convenient, high efficient method for the reduction of 4-azidonaphthalimide to 4-aminonaphthalimide (1) by using PMe3 has been developed. Several 4-substituted 1,8-naphthalimide iminophosphoranes were also successfully synthesized. Their structures were characterized by NMR and MS analyses. The structures of compounds 2 and 3 were also confirmed by single crystal X-ray diffraction analysis. Their optoelectronic properties of these naphthalimides were investigated. The results indicated that their optical properties could be tuned by different phosphine ligands, which make them novel potential organic luminescent materials.
- Xu, Shou De,Fang, Cheng Hui,Tian, Guang Xuan,Chen, Yi,Dou, Ye Hong,Kou, Jun Feng,Wu, Xiang Hua
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- The effects of varying the substituent and DNA sequence on the stability of 4-substituted DNA-naphthalimide complexes
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DNA duplexes are stabilized by many interactions, one of which is stacking interactions between the nucleic acid bases. These interactions are useful for designing small molecules that bind to DNA. Naphthalimide intercalators have been shown to be valuable anti-cancer agents that stack between the DNA bases and exhibit stabilizing effects. There is a continued need to design intercalators that will exhibit these stabilizing effects while being more selective toward DNA binding. This work investigates 4-substituted naphthalimides with varying functional groups and their interactions with nucleic acid duplexes. Mode of binding was determined via wavelength scans, circular dichroism, and viscosity measurements. Optical melting experiments were used to measure the absorbance of the sample as a function of temperature. The Tm values derived from the DNA duplexes were subtracted from the Tm values derived from the DNA-intercalator complexes, resulting in ΔTm values. The ΔTm values demonstrated that the substituents on the intercalator affect the stability of the DNA-intercalator complex. From the results of this study and comparison to results from previous work, we conclude that the substituent type and position on the core intercalator molecule affect the stability of the complex it forms with DNA.
- Jolley, Elizabeth A.,Hardebeck, Laura K.E.,Ren, Yi,Adams, Miranda S.,Lewis, Michael,Znosko, Brent M.
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- A GSH-responsive PET-based fluorescent probe for cancer cells imaging
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An efficient PET-based probe, in which the ferrocene quencher and the naphthalimide fluorophore are linked by a disulfide bond, has been developed. This probe can be activated by GSH with fluorescence a turn-on response for blocking the PET process. In addition, it was successfully applied for distinguishing cancer cells from normal cells
- Li, Xue,Wang, Huaying,Zhang, Youhui,Cao, Qianyong,Chen, Yong
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- A novel glutathione-Triggered theranostic prodrug for anticancer and imaging in living cells
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A novel theranostic prodrug was designed and synthesized by conjugating a naphthalimide derivative with Vitamin D2via a disulfide linker. The prodrug featured a highly selective detection process for glutathione (GSH) and showed a red-shifted f
- Zhang, Hengrui,Fang, Zhijie
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- Enhanced nonradiative decay in aqueous solutions of aminonaphthalimide derivatives via water-cluster formation
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The photophysics of two derivatives of 4-aminonaphthalimide have been studied in aqueous, ethanolic, and mixed aqueous/ethanolic solvents, including both normal and deuterated solvents. It is found that the fluorescence quantum yield and lifetime both decrease with increased water content of the solvent and that this is entirely due to increased nonradiative decay, the radiative rate constant being virtually independent of the solvent composition. It is proposed that a mechanism involving the formation of a hydrogen-bonded water cluster is responsible for the observed behavior with the excitation energy of the naphthalimide being distributed amongst the stretching vibrations of the water cluster. The increase in the rate of nonradiative decay is greatly reduced in deuterated solvent mixtures in accord with Siebrand's theory of radiationless processes.
- Yuan, Dongwu,Brown, Robert G.
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- Purification and characterization of a nitroreductase from the soil bacterium Streptomyces mirabilis
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A NADH-dependent nitroreductase from an efficient nitro-reducing soil bacterium, Streptomyces mirabilis DUT001, was isolated and characterized. The enzyme was purified to near homogeneity using ammonium sulfate precipitation, ion exchange chromatography, and gel filtration chromatography. The native enzyme was estimated by gel filtration to have a molecular weight of 68 kDa, and its subunit molecular weight determined by SDS-PAGE was about 34 kDa, which indicated this enzyme was a dimer. Polycyclic nitroaromatic compounds were preferred substrates for this enzyme. The purified enzyme exhibited maximum activity at pH 7.5 and 40 °C. The addition of various chemicals such as reducing agents, metal ions, and chelating agents, had effects on enzyme activity. Mg2+, Ca2+, Sr2+, and 1% (w/v) Triton X-100 increased activity. However, Hg2+, Co2+, Ni 2+, Cu2+, and SDS reduced activity. The maximum reaction rate (Vmax) was 64 μM min-1 mg-1 enzyme and the apparent Michaelis-Menten constants (Km) for 4-nitro-1,8- naphthalic anhydride and NADH were 276 and 29 μM, respectively. Menadione, bimethylenebis, sodium benzoate, and antimycin A were inhibitors of the purified nitroreductase with apparent inhibition constants (Kis) of 20, 36, 44 and 80 μM, respectively.
- Yang, Jun,Xie, Bo,Bai, Jing,Yang, Qing
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- A 4-aminonaphthalimide-based fluorescent traceable prodrug with excellent photoinduced cytotoxicity
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A blue light activated anti-cancer prodrug, NST, was designed based on a photoactive 4-aminonaphthalimide derivative and an anticancer drug, 10-hydroxycamptothecin. NST was hard to be taken up by living cells and showed negligible dark cytotoxicity. The irradiation caused photocleavage of NST and resulted in high cytotoxicity.
- Bing, Tao,Liu, Jing,Liu, Xiangjun,Shangguan, Dihua,Yi, Mengwen,Zhang, Lingling,Zhang, Nan,Zhong, Shilong
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supporting information
p. 6558 - 6561
(2021/07/07)
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- A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent
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Disseminated tumors lead to approximately 90% of cancer-associated deaths especially for hepatocellular carcinoma (HCC), indicating the imperative need of antimetastatic drugs and the ineffectiveness of current therapies. Recently polyamine derivatives have been identified as a promising prospect in dealing with metastatic tumors. Herein, a novel class of naphthalimide-polyamine conjugates 8a-8d, 13a-13c, 17 and 21 were synthesized and the mechanism was further determined. The polyamine conjugate 13b displayed remarkably elevated anti-tumor and anti-metastatic effects (76.01% and 75.02%) than the positive control amonafide (46.91% and 55.77%) at 5 mg/kg in vivo. The underlying molecular mechanism indicated that in addition to induce DNA damage by up-regulating p53 and γH2AX, 13b also targeted lysosome to modulate polyamine metabolism and function in a totally different way from that of amonafide. Furthermore, the HMGB1/p62/LC3II/LC3I and p53/SSAT/β-catenin pathways were mainly involved in the inhibition of 13b-induced HCC metastasis by targeting polyamine transporters (PTs) overexpressed in HCC. At last, 13b down-regulated the concentrations of Put, Spd and Spm by modulating polyamine metabolism key enzymes SSAT and PAO, which favored the suppression of fast growing tumor cells. Taken together, our study implies a promising strategy for naphthalimide conjugates to treat terminal cancer of HCC by targeting autophagy and tumor microenvironment with reduced toxicities and notable activities.
- Ma, Jing,Li, Linrong,Yue, Kexin,Zhang, Zhansheng,Su, Shihao,Chen, Yutong,Yu, Lu,Zhang, Pengfei,Ma, Ruijuan,Li, Yingguang,Ma, Yinxia,Jia, Huinan,Wang, Chaojie,Wang, Jiajia,Xie, Songqiang
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- Distinguished Cys. Hcy And GSH naphthalimide fluorescent probe as well as preparation method and application thereof
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The naphthalimide fluorescent probe can be used for distinguishing Cys, Hcy and GSH naphthalimide fluorescent probe as well as a preparation method and application thereof, and particularly relates to a fluorescence probe (Z1, Z2) for detecting a biological thiol through a urethane linker. The probe itself has blue fluorescence, emits yellow-green fluorescence with longer wavelength after the action of Cys and Hcy, and can realize distinguishing detection of Cys, Hcy and GSH. The fluorescent probe Z1, Z2 pairs Cys are high in action speed, strong in selectivity and high in sensitivity, can be used for detecting and imaging intracellular cysteine, and is simple in synthesis method, accessible in raw materials and easy to popularize.
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Paragraph 0032; 0033
(2021/09/08)
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- Tetravalent platinum naphthalimide complex, preparation method and application thereof
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The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tetravalent platinum naphthalimide complex, a preparation method and application thereof. The tetravalent platinum naphthalimide complex has good anti-tumor activity, which is better than that of cis-platinum and oxaliplatin, and the tetravalent platinum naphthalimide complex has better stability than bivalent platinum like cis-platinum, carboplatin and oxaliplatin. According to the invention, the naphthalimide modified tetravalent platinum has good targeting performance on tumor cells, high selectivity on tumor cells is improved, and different from a classic divalent platinum drug, the complex provided by the invention regulates and controls subcellular organelles and cell nucleus functionsto reverse drug resistance by targeting a tumor high polyamine microenvironment, and relieves immunosuppression of T cells around tumors at the same time. The complex provided by the invention also solves the problems of poor solubility, tedious clinical compatibility, poor patient immunity in clinical application of chemotherapeutic drugs and the like of previous bivalent platinum antitumor drugs, and has good fat solubility and water solubility.
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Paragraph 0095; 0099-0101; 0109; 0113-0115; 0123; 0127-0129
(2020/07/21)
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- A two-photon fluorescence self-reporting black phosphorus nanoprobe for the: In situ monitoring of therapy response
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The in situ and real-time supervision of reactive oxygen species (ROS) generated during photodynamic therapy (PDT) is of great significance for lessening nonspecific damage and guiding personalized therapy. However, photosensitizers frequently fail to deliver successful treatment accompanying the ROS-related imaging signals produced, impeding simple treatment outcome predictions and therapeutic schedule adjustments. Here, we report a two-photon fluorescence self-reporting strategy for the in situ and real-time monitoring of treatment response via a novel black phosphorus-based two-photon nanoprobe (TPBP). TPBP effectively generated singlet oxygen (1O2) under near-infrared laser irradiation for PDT, and 1O2 stimulated a two-photon molecule to emit fluorescence signals for feedback of 1O2 generation, which facilitated the regulation of treatment parameters to achieve precise and personalized medicine in deep tissue. This journal is
- Guan, Kesong,Wang, Peng,Zhou, Fang,Wang, Youjuan,Liu, Hong-Wen,Xie, Qingji,Song, Guosheng,Yin, Xia,Huan, Shuangyan,Zhang, Xiao-Bing
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supporting information
p. 14007 - 14010
(2020/11/21)
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- A class of stable nitroxide free radical modified naphthalimide compounds, and application thereof
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The invention belongs to the technical field of medicines, and relates to a class of naphthalimide compounds modified by stable nitroxide free radicals, and application thereof, particularly to a class of naphthalimide compounds with stable nitroxide free radicals, and application of the naphthalimide compounds in preparation of antitumor medicines. According to the invention, stable nitroxide free radicals are introduced into a naphthalimide parent structure to obtain a naphthalimide compound represented by a general formula I or II, and a pharmaceutically acceptable salt, a solvate and a hydrate thereof, wherein R1, R2, R3 and R4 are defined in the claims and the specification.
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Paragraph 0064-0065
(2020/07/02)
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- Fluorogenic iminosydnones: Bioorthogonal tools for double turn-on click-and-release reactions
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In this article, we report the synthesis and use of iminosydnone-based profluorophores as bioorthogonal cleavable linkers for imaging applications. These linkers react with cycloalkynes via subsequent [3+2] cycloaddition and retro Diels-Alder reactions, allowing simultaneous release of two dyes in biological media. This journal is
- Audisio, Davide,Porte, Karine,Riomet, Margaux,Taran, Frédéric,Wijkhuisen, Anne
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supporting information
p. 7183 - 7186
(2020/07/14)
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- A used for protein labeling and detection of the fluorescent probe and its synthetic method and application
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The invention provides fluorescent probes used for protein labeling and detection, and a synthetic method and application thereof. The probes are prepared by reacting 4-bromo-1,8-naphthalic anhydride with sodium azide, sodium sulfide nonahydrate, acetyl chloride, diethylamine and like. The structure of the probes are as described in the specification; and R in the structure of the probe is a probe 1 as described in the specification or a probe 2 as described in the specification. The synthetic method is simple to operate and uses cheap raw materials. The probes emit blue fluorescent light with a wavelength of ~460 nm in an aqueous solution and emits green to yellow fluorescent light with a wavelength of 525 to 560 nm in polar solvents like methanol, dimethyl sulfoxide, N,N-dimethyl formamide and ethanol. After the probes are introduced into SNAP-tag protein, the fluorescence intensity of the probe is obviously enhanced, and the fluorescence ratio of the probe at positions of long wavelength (~550 nm) is obviously increased. The probes can be applied to fields like protein labeling and detection, biological fluorescence imaging, etc.
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Paragraph 0045; 0049-0051
(2019/02/08)
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- Anticancer activity and topoisomerase II inhibition of naphthalimides with Ω-hydroxylalkylamine side-chains of different lengths
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Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Method: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 μM to 7 μM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 μM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.
- Kasprzycki, Przemys?aw,Strama, Klaudia,Tomczyk, Mateusz D.,Walczak, Krzysztof Z.,Wawszków, Martyna,Wyrostek, Anna Byczek
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p. 550 - 560
(2019/07/12)
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- Detecting tumor hypoxic compound and its preparation method
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The invention relates to a compound for detecting tumor hypoxia disclosed as Formula I, a preparation method and application thereof, and a kit containing the compound. The groups in the formula are disclosed in the specification. The compound can be used for detecting hypoxia of tumor tissues, can respond to changes of partial oxygen pressure and reducibility of partial tissues, and provides conditions for early detection of cancers. The compound has the advantages of novel structure, simple synthesis process, high detection sensitivity, high fluorescence enhancement multiple, no trauma and the like, and can be used for cell detection and even living body detection.
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Paragraph 0088; 0089; 0090
(2019/01/16)
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- Fluorescent probe for intracellular protein labelling as well as synthesis method and application of fluorescent probe
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The invention provides a fluorescent probe for intracellular protein labelling as well as a synthesis method and an application of the fluorescent probe. The provided probe is synthesized in simple steps and has good light stability. Compared with existing fluorescent probes for cell labeling, the probe can be specifically bound with SNAP labels in a complicated system and label any protein in cells. The probe can be applied to detection of copper ions in the cells, fluorescence gradually disappears with increase of the concentration of the copper ions, and the copper ion detection function isrealized. The probe realizes labeling of any protein and detection of the copper ions in the complicated environment and has very important application value in the biological and medical fields.
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Paragraph 0011; 0048; 0051; 0052
(2018/06/04)
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- A reduction-responsive liposomal nanocarrier with self-reporting ability for efficient gene delivery
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In the past few decades, although various reduction-responsive nanocarriers have been designed and explored for gene delivery, it is difficult to directly detect or monitor the reduction capability of these carriers, especially under intracellular conditions. Taking advantage of the generated fluorescence signal in the reduction process of the naphthalimide-sulfonamide (NS) group, we developed a novel liposomal nanocarrier, FNSL, which showed reduction-sensitive property and self-reporting character. As a new reduction-responsive site in a gene delivery system, the NS group in FNSL is capable of responding to glutathione (GSH) and simultaneously emitting green fluorescence at 500 nm in both extra- and intracellular circumstances. Hence, it will be very convenient to assess the reducibility of this carrier and monitor the stimuli-responsive gene release via fluorescence signal. FNSL has high affinity for DNA and can condense it into nanoparticles with a proper nano-size and zeta potential. Compared with the non-reducible FNAL, FNSL showed enhanced gene release capability, higher transfection efficiency (TE), and lower cytotoxicity. Furthermore, treatment of FNSL-mediated transfection with slightly exogenous GSH greatly improved the TE of FNSL in HepG2 cells, and its TE was even higher than that of Lipofectamine 2000. These results demonstrate that FNSL possesses great potential for efficient and low-toxicity gene delivery, and this study on a bioreducible liposome with self-reporting ability would be a guide for further research on the development of biodegradable gene carriers.
- Wang, Bing,Zhang, Ji,Liu, Yan-Hong,Zhang, Wei,Xiao, Ya-Ping,Zhao, Rui-Mo,Yu, Xiao-Qi
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supporting information
p. 2860 - 2868
(2018/05/23)
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- The environmental-sensitivity of a fluorescent ZTRS-Cd(ii) complex was applied to discriminate different types of surfactants and determine their CMC values
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We have, for the first time, reported a fluorescent probe (ZTRS-C18-Cd(ii) complex) which discriminated four types of surfactants. This recognition was realized depending on the transformation of ZTRS-Cd2+ binding patterns in different microenvironments formed in various types of surfactants.
- Deng, Fei,Long, Shuangshuang,Qiao, Qinglong,Xu, Zhaochao
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p. 6157 - 6160
(2018/06/18)
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- A Naphthalimide-Based Cd2+Fluorescent Probe with Carbamoylmethyl Groups Working as Chelators and PET-Promoters under Neutral Conditions
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We have developed a novel naphthalimide-based Cd2+fluorescent probe (1), featuring almost no background response, high sensitivity and selectivity toward Cd2+through its high association constant [K=(2.10±0.423)×106], and a practical working pH range. Membrane-permeability was conferred on 1 by replacing the imide and amide substituents with n-butyl groups, and hence the derivative (4) has found practical utility on fluorescent imaging of Cd2+in HeLa cells. Comparison of fluorescent properties between various compounds derived from 1 has demonstrated that the carbamoylmethyl groups in 1 function not only as Cd2+chelators but also as promoters for photoinduced electron transfer (PET) by lowering the basicity of the two tertiary amino groups. As a result, 1 and 4 exhibited highly practical performance as Cd2+probes under neutral conditions.
- Tsukamoto, Koji,Shimabukuro, Shota,Mabuchi, Miyuki,Maeda, Hatsuo
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supporting information
p. 8579 - 8585
(2016/07/07)
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- Synthesis and Photophysical Studies on Naphthalimide Derived Fluorophores as Markers in Drug Delivery
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Derivatives of 4-amino-1,8-naphthalimide containing a free alkyl chain bearing carboxyl group as linker and different substituents at 4-amino function have been synthesized, characterized and studied for their photophysical properties. Steady state fluorescence studies showed quantum yield varied from 0.45 to 0.65 with Stokes shift in the range of 5824–8558?cm?1. Spectroscopic and physicochemical parameters, like electronic absorption, emission, and extinction coefficient were investigated in order to explore the analytical potential of compounds. Solvatochromic studies demonstrated that all compounds were sensitive towards the polarity of different solvents showing the highest degree of fluorescence in acetonitrile. In addition, the compounds in the presence of ions, viz. Na+, K+ and Mg2+ at concentration of 0.1–2 equivalents, showed a decreasing trend in fluorescence with increasing ionic concentration. TCSPC set – up was used to measure the fluorescence lifetime of compounds, which was found to be bi-exponential with longer and shorter component at their respective amplitudes. The average lifetime of compounds was observed to be 5.76–9.96?ns indicating the possibility of their greater utilization in research and diagnosis.
- Singh, Nidhi,Srivastava, Ritika,Singh, Anuradha,Singh, Ramendra K.
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p. 1431 - 1438
(2016/07/30)
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- Pyrimidine naphthalimide derivatives, and preparation method and application thereof
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The invention discloses a kind of pyrimidine naphthalimide derivatives, and a preparation method and application thereof. The derivatives have structures shown as formulas I to III shown as the accompanying drawing. In the formulas I, II and III, a is 0 or 1 or 2; m is 2 or 3 or 4; n is 2 or 3 or 4; x is an integer being 0 to 6; R1 is shown as the accompanying drawing; R2 is shown as the accompanying drawing; R3 is shown as the accompanying drawing. The invention provides a preparation method for building pyrimidine naphthalimide through introducing o-amino cyanogens by using acenaphthene as raw materials. According to the existing data, after the modification by polyamine with targeted carrying capability, the antitumor activity of naphthalimide is obviously improved; a strong inhibition effect is achieved on tumor transfer. According to the discovery, a series of pyrimidine naphthalimide derivatives are designed and synthesized. According to the display by primary test results, the kind of pyrimidine naphthalimide derivatives show good antitumor effect in vitro on various tumor cell strains. The important significance is realized on developing novel anti-tumor medicine.
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- Visible-light-induced cleavage of 4-α-amino acid substituted naphthalimides and its application in DNA photocleavage
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A new kind of visible-light photocleavable molecule, 4-α-amino acid substituted naphthalimide, is reported. The cleavage occurred at the C-N bond between the 4-amino and the amino acid residue and released a 4-aminonaphthalimide. A lysine substituted naphthalimide exhibited a strong DNA photocleavage activity when irradiated with a blue light LED. This journal is
- Zhou, Jin,Fang, Canliang,Liu, Ying,Zhao, Yao,Zhang, Nan,Liu, Xiangjun,Wang, Fuyi,Shangguan, Dihua
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supporting information
p. 3931 - 3935
(2015/03/30)
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- 1,8-Naphthalimide derivatives: New leads against dynamin i GTPase activity
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Fragment-based in silico screening against dynamin I (dynI) GTPase activity identified the 1,8-naphthalimide framework as a potential scaffold for the design of new inhibitors targeting the GTP binding pocket of dynI. Structure-based design, synthesis and subsequent optimization resulted in the development of a library of 1,8-naphthalimide derivatives, called the Naphthaladyn series, with compounds 23 and 29 being the most active (IC50 of 19.1 ± 0.3 and 18.5 ± 1.7 μM respectively). Compound 29 showed effective inhibition of clathrin-mediated endocytosis (IC50(CME) 66 μM). The results introduce 29 as an optimised GTP-competitive lead Naphthaladyn compound for the further development of naphthalimide-based dynI GTPase inhibitors.
- Abdel-Hamid, Mohammed K.,Macgregor, Kylie A.,Odell, Luke R.,Chau, Ngoc,Mariana, Anna,Whiting, Ainslie,Robinson, Phillip J.,McCluskey, Adam
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p. 8016 - 8028
(2015/07/27)
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- Highly selective off-on fluorescent probe for imaging thioredoxin reductase in living cells
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The first fluorescent probe for mammalian thioredoxin reductase (TrxR), TRFS-green, was designed, synthesized, and fully evaluated. The probe features a 1,2-dithiolane scaffold with a quenched naphthalimide fluorophore. TRFS-green displays a green fluorescence off-on change induced by the TrxR-mediated disulfide cleavage and subsequent intramolecular cyclization to liberate the masked naphthalimide fluorophore. It was demonstrated in vitro that TRFS-green manifests high selectivity toward TrxR over other related enzymes and various small molecule thiols as well as biological reducing molecules. HPLC analyses indicated that TRFS-green was exclusively converted to naphthalimide catalyzed by TrxR. The ability in triggering on the fluorescence signal by cellular protein extracts correlates well with the endogenous TrxR activity in different cells. Furthermore, inhibition of TrxR by 2,4-dinitrochlorobenzene or depletion of TrxR by immunoprecipitation remarkably decreases the reduction of TRFS-green by cellular protein extracts. Finally, TRFS-green was successfully applied in imaging TrxR activity in living cells. The fluorescence signal of TRFS-green in living cells was inhibited by pretreating the cells with TrxR inhibitor in a dose-dependent manner, potentiating the development of living cell-based screening assay for identifying TrxR inhibitors. We expect the novel fluorescent probe TRFS-green would facilitate the discovery of TrxR-targeting small molecules for potential therapeutic agents and provide significant advances in understanding the physiological/pathophysiological functions of TrxR in vivo.
- Zhang, Liangwei,Duan, Dongzhu,Liu, Yaping,Ge, Chunpo,Cui, Xuemei,Sun, Jinyu,Fang, Jianguo
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p. 226 - 233
(2014/01/23)
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- Dithiaarsanes induce oxidative stress-mediated apoptosis in HL-60 cells by selectively targeting thioredoxin reductase
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The selenoprotein thioredoxin reductase (TrxR) plays a pivotal role in regulating cellular redox homeostasis and has attracted increasing attention as a promising anticancer drug target. We report here that 2-(4-aminophenyl)-1,3,2- dithiarsinane (PAO-PDT, 4), a potent and highly selective small molecule inhibitor of TrxR, stoichiometrically binds to the C-terminal selenocysteine/cysteine pair in the enzyme in vitro and induces oxidative stress-mediated apoptosis in HL-60 cells. The molecular action of 4 in cells involves inhibition of TrxR, elevation of reactive oxygen species, depletion of cellular thiols, and activation of caspase-3. Knockdown of TrxR sensitizes the cells to 4 treatment, whereas overexpression of the functional enzyme alleviates the cytotoxicity, providing physiological relevance for targeting TrxR by 4 in cells. The simplicity of the structure and the presence of an easily manipulated amine group will facilitate the further development of 4 as a potential cancer chemotherapeutic agent.
- Liu, Yaping,Duan, Dongzhu,Yao, Juan,Zhang, Baoxin,Peng, Shoujiao,Ma, Huilong,Song, Yanlin,Fang, Jianguo
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p. 5203 - 5211
(2014/07/08)
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- Development of 1,8-naphthalimides as clathrin inhibitors
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We reported the first small molecule inhibitors of the interaction between the clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin inhibition1). Initial screening of a ~17 000 small molecule ChemBioNet library identified 1. Screening of an existing in-house propriety library identified four substituted 1,8-napthalimides as ~80-120 μM clathrin inhibitors. Focused library development gave 3-sulfo-N-(4-aminobenzyl)- 1,8-naphthalimide, potassium salt (18, IC50 ≈ 18 μM). A second library targeting the 4-aminobenzyl moiety was developed, and four analogues displayed comparable activity (26, 27, 28, 34 with IC50 values of 22, 16, 15, and 15 μM respectively) with a further four (24, 25, 32, 33) more active than 18 with IC50 values of 10, 6.9, 12, and 10 μM, respectively. Docking studies rationalized the structure-activity relationship (SAR) with the biological data. 3-Sulfo-N-benzyl-1,8-naphthalimide, potassium salt (25) with an IC50≈ 6.9 μM, is the most potent clathrin terminal domain-amphiphysin inhibitor reported to date.
- Macgregor, Kylie A.,Robertson, Mark J.,Young, Kelly A.,Von Kleist, Lisa,Stahlschmidt, Wiebke,Whiting, Ainslie,Chau, Ngoc,Robinson, Phillip J.,Haucke, Volker,McCluskey, Adam
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p. 131 - 143
(2014/02/14)
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- Slipping synthesis of cucurbit[7]uril-based [2]rotaxane in organic environment
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A dumbbell molecule with one naphthalimide and one isophthalic acid stoppers was synthesized and could fold into the cavity of cucurbit[7]uril (CB[7]) in formic acid to form a 1:1 complex. Once the solution of the complex was heated, the CB[7] ring would slip over the isophthalic acid unit, producing a stable [2]rotaxane. The energy barrier (H?) of this slippage was estimated as 109 kJ mol-1.
- Huang, Xinghua,Huang, Shiyao,Zhai, Baoqi,Zhang, Yu,Xu, Yanan,Wang, Qiaochun
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p. 6414 - 6417
(2013/01/15)
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- The synthesis and fluorescence of novel N-substituted-1,8-naphthylimides
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(Chemical Equation Presented) The synthesis and characterisation of a series of novel 4-acylamino and 4-alkylamino-N-1,8-naphthalimides is described. The UV-visible absorption and emission properties of the compounds are reported. Significant solvent effects are noted for 4-n-butyl-9-n-butyl-1,8- naphthylimide. The incorporation of acetyl and chloroacetyl groups into the 4-substituent markedly increases the fluorescence quantum yield compared with 4-alkylamino substituemnts.
- Yuan, Dongwu,Brown, Robert G.,Hepworth, John D.,Alexiou, Michael S.,Tyman, John H. P.
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p. 397 - 404
(2008/09/20)
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- Highly chemoselective reduction of aromatic nitro compounds to the corresponding hydroxylamines catalysed by plant cells from a grape (Vitis vinifera L.)
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Cells from a grape (Vitis vinifera L.) reduce aromatic nitro compounds under mild conditions to the corresponding hydroxylamines with unprecedented chemoselectivity. The Royal Society of Chemistry 2005.
- Li, Feng,Cui, Jingnan,Qian, Xuhong,Zhang, Rong,Xiao, Yi
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p. 1901 - 1903
(2007/10/03)
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- A novel strategy for the preparation of arylhydroxylamines: Chemoselective reduction of aromatic nitro compounds using bakers' yeast
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Using bakers' yeast as a biocatalyst, the chemoselective reduction of aromatic nitro compounds bearing electron-withdrawing groups gave the corresponding hydroxylamines with good to excellent conversion under mild conditions.
- Li, Feng,Cui, Jingnan,Qian, Xuhong,Zhang, Rong
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p. 2338 - 2339
(2007/10/03)
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- Azo-functionalized dendrimers
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We report the synthesis of azo-functionalized Starburst polyamidoamine (PAMAM) dendrimers. The following three systems of azo-functionalized PAMAM dendrimers were prepared by different synthetic routes: (i) phenylazo derivatives; (ii) naphthalimide azo derivatives; and (iii) phthalimide azo derivatives. Model compounds in each system were synthesized for spectroscopic comparison. Confirmation of structure was achieved using a combination of NMR and IR spectroscopy to ascertain the functional sites (i.e., the azo and the cyclic imides), while mass spectrometry and UV-vis spectrophotometry were employed to ascertain the extent of functionalization. Substitution by the azo pendent groups increased the thermal stability of PAMAM dendrimers (TGA weight loss of the naphthalimide azo-functionalized PAMAM dendrimers up to 300°C, ca. 5%).
- Cheon, Kap-Soo,Kazmaier, Peter M.,Keum, Sam-Rok,Park, Kuk-Tae,Buncel, Erwin
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p. 551 - 566
(2007/10/03)
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- Syntheses, characterisation and fluorescence study of some novel naphthalimide derivatives
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Three fluorescent derivatives viz. 4-tosylamido-1,8-naphthalic anhydride, 4-dansylamido-1,8-naphthalimido-N-pentanol and 4-dabsylamido-1,8-naphthalimido-N-pentanol have been prepared and characterised. The comparative fluorescence studies and quantum yield estimation has been carried out in different solvents such as methanol, dioxane, water, water-methanol gradient, normal aqueous solutions of sodium carbonate, hydrochloric acid and buffers like ammonium acetate, 1 X TRIS-EDTA and the effect of inorganic salts like sodium chloride, potassium chloride, magnesium sulphate has also been studied. Thus, optimal conditions for maximum fluorescence yield has been worked out. The fluorescent derivatives reported herein have the potential to be used for covalent as well as non-covalent labelling of various biomolecules, specially to synthetic oligonucleotides. The labelled oligonucleotides have been proved to be of immense value as probes in clinical diagnostics.
- Singh, Yashveer,Misra, Arvind,Misra, Krishna
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p. 1238 - 1245
(2007/10/03)
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- Isoquinolones
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Benzo[de]isoquinoline-1,3-dione of Formula or a pharmaceutically acceptable salt thereof wherein R is hydrogen or a protecting group typically used in the art for protecting alcohols and R1-R5are each independently chosen from H, Cl, Br, F, straight or branched alkyl C1-C8alkyl, C3-C8cycloalkyl, heterocycle or bridged heterocycle of 4-9 atoms containing 1-3 heteroatoms, —(CR′2)nOR6, —(CR′2)nN(R6)2, —(CR′2)nNR6COR7, —(CR′2)nNR6SO2OR7, —(CR′2)nNR6SO2N(R6)2, —(CR′2)nOSO2N(R6)2, —(CR′2)nCN, —(CR′2)n(NOR6)R7, NO2, CF3, —(CR′2)nSOmR7, —(CR′2)nSOmR7, —(CR′2)nCO2R6, —(CR′2)nCON(R6)2, Ph, and any two of R1-R5may form a substituted or unsubstituted ring of 5-7 total atoms having 0-2 heteroatoms are claimed which are selective inhibitors of bacterial DNA gyrase and DNA topoisomerase useful in antibacterial agents. Methods for their preparation and formulation as well as novel intermediates useful in the preparation of the final products are also claimed.
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- The Synthesis of Alkylamino-N-alkylnaphthalic-1,8-imides from 2- and 4-nitronaphthalic Anhydrides by Nitro group Displacement
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4-Alkylamino-N-alkylnaphthalic-1,8-imides and 2-alkylamino isomers have been synthesised by the reaction of 4-nitro- and 2-nitronaphthalic anhydrides respectively with primary amines in aprotic solvents in which reaction the nitro group in 3-nitronaphthalic anhydride is unreactive. Unsymmetrical compounds in the 2- and 4-series are derived from either the appropriate 4-nitro-N-alkylnaphthalic-1,8-imide or for 4-dilakylamino compounds from 4-nitronaphthalic anhydride by reaction with a secondary amine and then the 4-dialkylaminonaphthalic anhydride with a primary amine.
- Alexiou, Michael S.,Tyman, John H. P.
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p. 632 - 652
(2007/10/03)
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- The UV-Visible Absorption and Fluorescence of some Substituted 1,8-Naphthalimides and Naphthalic Anhydrides
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A number of substituted 1,8-naphthalimides and naphthalic anhydrides have been prepared and their absorption and fluorescence properties in absolute ethanol have been determined.In the absence of an alkylamino substituent in the naphthalene ring, the compounds are colourless and weakly fluorescent.In the presence of such a substituent they become yellow and frequently fluoresce strongly with quantum yields of the order of 0.8.
- Alexiou, Michael S.,Tychopoulos, Vasiliki,Ghorbanian, Shohreh,Tyman, John H. P.,Brown, Robert G.,Brittain, Patrick I.
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p. 837 - 842
(2007/10/02)
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