The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Ac r_3-NLS, by conjuga...The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Ac r_3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence(NLS), a short cationic peptide. To further improve the antimicrobial activity of our agent, dimeric(Acr_3-NLS)_2 was simultaneously synthesized by joining two monomeric Acr_3-NLS together via a disulfide linker. Our results show that Acr_3-NLS and especially(Acr_3-NLS)_2 display signifi cant antimicrobial activity against gramnegative and gram-positive bacteria compared to that of the NLS. Subsequently, the results derived from the study on the mechanism of action demonstrate that Acr_3-NLS and(Acr_3-NLS)_2 can kill bacteria by membrane disruption and DNA binding. The double targets—cell membrane and intracellular DNA—will reduce the risk of bacteria developing resistance to Acr_3-NLS and(Acr_3-NLS)_2. Overall, this study provides a novel strategy to design highly eff ective antimicrobial agents with a dual mode of action for infection treatment.展开更多
Zirconia nanotube array films(ZNAF)prepared by anodic oxidation method were used as immobilization materials for acridine orange(AO),rhodamine B(RB)and AO-RB systems.A comparative study on their fluorescence emission ...Zirconia nanotube array films(ZNAF)prepared by anodic oxidation method were used as immobilization materials for acridine orange(AO),rhodamine B(RB)and AO-RB systems.A comparative study on their fluorescence emission intensity,fluorescence resonance energy transfer(FRET)and fluorescence detection of nitrite in aqueous solutions and on immobilization films with ZNAF as carriers was carried out.Results demonstrate that the solution pH values and immobilization on ZNAF have a great influence on the per-formance of these fluorescent molecules.Compared with aqueous solutions,the fluorescence emission in-tensity of AO and RB is considerably increased by immobilization,which is 8.0 and 4.2 times higher than the original,respectively.The energy transfer efficiency(E)of the AO-RB system increases from 40.9%to 84.8%by loading it on ZNAF.Moreover,after immobilization onto ZNAF,the fluorescence detection performance of nitrite is also significantly improved.The limit of detection decreases from 0.95 ng/mL to 0.22 ng/mL and the sensitivity increases from 939.18 to 15,031.68 mL/μg through loading AO onto ZNAF.展开更多
We have developed an on-line detection method using acridine orange as the fluorescence probe and applied this method to rapidly identify active compounds in herbal medicines. This on-line method was equipped with a h...We have developed an on-line detection method using acridine orange as the fluorescence probe and applied this method to rapidly identify active compounds in herbal medicines. This on-line method was equipped with a high-performance liquid chromatography tandem diode array detector, electrospray ionization-ion-trap time-of-flight mass spectrometry and DNA- acridine orange fluorescence detection （HPLC-DAD-MSn-DNA-AO-FLD）. A large amount of information could be simultaneously obtained during one run, which included HPLC fingerprint, ultraviolet spectra, total ion chromatograms, MSn data of high-resolution mass spectrometry and activity profile of each compound binding with DNA. The method also provided information on structureactivity relationships and mechanism of interaction. We used this on-line method to identify five DNA-binding activity components from Lithospermum erythrorhizon sample for the first time. The result showed that the parent nucleus of shikonin derivatives could bind with DNA. The structure-activity relationship showed that the parent nucleus of shikonin derivatives plays a major role in DNA binding, not the carboxyl group on the side chain. This simple, rapid, high precision and good stability on-line method should be useful for compound separation, structural identification and screening of DNA-binding compounds in herbal medicines.展开更多
In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells p...In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation.In addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory activities.Subsequent mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells.Our study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.展开更多
A new photocatalyst, TiO_2 powder immobilized on polystyrene (PS) thin films,was prepared using a novel method and its photocatalytic activity on the photodegradation ofacridine dye in aqueous solution was tested. By ...A new photocatalyst, TiO_2 powder immobilized on polystyrene (PS) thin films,was prepared using a novel method and its photocatalytic activity on the photodegradation ofacridine dye in aqueous solution was tested. By this method, the crystal form and grain size of theimmobilized TiO_2 were well maintained. Compared with TiO_2 powder, the photocatalytic activity ofTiO_2/PS thin films was not significantly reduced. The catalyst is stable and can be reused severaltimes without the loss of activity, which makes wastewater treatment using this photocatalyticdegradation technique of this way possible in the practical application.展开更多
Hydrogen has been deemed as one of the most efficient energy carriers for a broad variety of industrial applications[1,2].Large-scale,low-cost hydrogen production,safe storage and delivery represent a tremendous techn...Hydrogen has been deemed as one of the most efficient energy carriers for a broad variety of industrial applications[1,2].Large-scale,low-cost hydrogen production,safe storage and delivery represent a tremendous technological challenge and have become a subject of intense research and development activities in the past few decades[3–5].展开更多
Graphene/acridine （G-Acr） hybrid structures were synthesized through covalent functionalization of graphene oxide with 9-（4- aminophenyl）acridine （APA） and its derivatives. The G-Act hybrids were characterized b...Graphene/acridine （G-Acr） hybrid structures were synthesized through covalent functionalization of graphene oxide with 9-（4- aminophenyl）acridine （APA） and its derivatives. The G-Act hybrids were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, thermal gravimetric analysis and Raman spectroscopy. X-ray photoelectron spectroscopy confirms that the binding energies of APA and its derivatives shifted to higher values, revealing pronounced charge transfer at the interface of graphene and organic molecules.展开更多
Objeαive： To determine whether Interferon-alpha-2b （IFN-α2b） can modulate the autophagic response in hepatocellular carcinoma cells. Methods： Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy ...Objeαive： To determine whether Interferon-alpha-2b （IFN-α2b） can modulate the autophagic response in hepatocellular carcinoma cells. Methods： Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission eleαron microscopy and immunoblotting. Results： Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. The acridine orange HepG2 cell ratios were （4.3±1.0）%, （6.9±1.4）%, and （13.1±2.3）%, respeαively, after treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punαate pattern was observed in HepG2 cells treated with 10,000 IU/mL [FN-α2b for 48 h, but only diffuse and weakly fluorescent GFP-LC3 punαa was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like charaαeristics, including single- or double-membrane vacuoles containing intaα and degraded cellular debris. The Beclinl and LC3-II protein expression was up-regulated by IFN-α2b treatment. Conclusion： Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclinl signaling pathway was stimulated by IFN-α2b.展开更多
Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series ...Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues,LXL 1-5,were synthesized and their antiproliferative activity against HepC-2 cell lines were evaluated,among which the 9-benzyloxyacridine analogue,LXL-5, showed inhibitory activity against tyrosine kinases,VEGFR-2 and Src.The results of UV-visible absorption spectra and fluorescence emission spectra,as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity.Our study suggested that acridine scaffold,previously shown to have no multi-target kinase and topoisomerase inhibitory activity,might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.展开更多
Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and He...Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.展开更多
Objective To estimate the predictive value of double fluorescence [acridine orange （AO）/propidium iodide （PI）] staining results for fertilization rate and clinical outcomes and analyze the correlation between th...Objective To estimate the predictive value of double fluorescence [acridine orange （AO）/propidium iodide （PI）] staining results for fertilization rate and clinical outcomes and analyze the correlation between the results of AO/P1 staining and sperm apoptosis. Methods A prospective study was carried out, 235 infertile couples remedied using traditional in vitro fertilization （IVF） were included. Semen collected from 235 patients were stained by fluorescence dye, AO and PL at the same time the spermatozoa apoptosis rate was calculated by using flow cytometry to detect the rate of Annexin V＋/ PI- . The result of fluorescence was divided into 3 groups as green （G）, yellow （Y） and red （R） according to the color of fluorescence. The correlation between the percent of the 3 colors and clinical outcomes and spermatozoa apoptosis rate was evaluated. Results Significant negative correlation was observed between the percentage of Y and fertilization rate （r= -0.42, P=0.04）, no significant correlation was observed between the percentage of G, R and fertilization rate. The percentage of G, Y, R was not significantly different between pregnant patients and non-pregnant patients, respectiw,ly, while the percentage of Y was significant different between miscarriage patients and liveborn patients （r=0.6L P=0.01） and no significant difference exist in the percentage of G and R between liveborn patients and miscarriage patients. There was a significant positive correlation between the percentage of Y and the rate of Annexin V＋/ PI （r=0.53, P=0.04）, and no significant correlation was shown between the percentage of G, R and the rate of Annexin V＋/ PI-.Conclusion The percentage of yellow group of double fluorescence （AO/PI） staining will affect the fertilization rate and the miscarriage rate, and this group of spermatozoa may be connected with the spermatozoa apoptosis.展开更多
Objective:To evaluate new compounds synthesized by integrating quinoline,quinazoline,and acridine rings with the active moiety of(5-nitroheteroaryl)methylene hydrazine.Methods:A new series of compounds(1a,1b,2a,2b,3a,...Objective:To evaluate new compounds synthesized by integrating quinoline,quinazoline,and acridine rings with the active moiety of(5-nitroheteroaryl)methylene hydrazine.Methods:A new series of compounds(1a,1b,2a,2b,3a,and 3b)were synthesized and evaluated for cytotoxicity against COS-7 cells using the MTT assay.In vitro anti-plasmodial activity of the compounds was measured against CQ-sensitive(3D7)and CQ-resistant(K1)Plasmodium(P.)falciparum strains.β-hematin assay was performed to assess the inhibitory effects ofβ-hematin formation for new compounds.Results:The synthetic compounds had anti-plasmodial activity against blood-stage of 3D7[IC50=(0.328-5.483)μM]and K1[IC50=(0.622-7.746)μM]strains of P.falciparum,with no cytotoxicity against COS-7 cells in effective doses.Compounds 1a,1b,and 2b were the most effective derivatives against P.falciparum 3D7 and K1 strains.Based on theβ-hematin assay,the inhibition ofβ-hematin formation is the main mechanism of the inhibitory effect of these compounds.Conclusions:The synthetic compounds could inhibit the erythrocytic stages of CQ-sensitive and resistant P.falciparum strains without toxicity towards mammalian cells.Compounds 1b,2a,and 2b had comparable anti-plasmodial activity against both CQ-sensitive(3D7)and resistant(K1)P.falciparum strains.These compounds may be promising lead structures for the development of new anti-malarial drugs.展开更多
Under microwave irradiation, the one-pot multicomponent condensation reaction of three moles of aromatic aldehydes with two moles of cyclic ketones having free a,a＇-methylene positions such as cyclopentanone or cyclo...Under microwave irradiation, the one-pot multicomponent condensation reaction of three moles of aromatic aldehydes with two moles of cyclic ketones having free a,a＇-methylene positions such as cyclopentanone or cyclohexanone in the presence of ammonium acetate and acetic acid afforded dicycloalkenopyridines with two a-arylidene groups in high yields. Under the similar reaction condition, the reaction of aromatic aldehydes with 1-tetralone having only one a-methylene position alternatively resulted in 10-aryl-2,3：5,6-dibenzoacridines.展开更多
The N-cyclopropyl-9-（3,4-dicholophenyl）- 1,2,3,4,5,6,7,8,9,10-decahydroacri- dine-1,8-dione was synthesized by the reaction of 1,3-cyclohexanedione, N-cyclopropylamine and 3,4-dicholoaldehyde in water and glycol und...The N-cyclopropyl-9-（3,4-dicholophenyl）- 1,2,3,4,5,6,7,8,9,10-decahydroacri- dine-1,8-dione was synthesized by the reaction of 1,3-cyclohexanedione, N-cyclopropylamine and 3,4-dicholoaldehyde in water and glycol under microwave irradiation. Its crystal structure was determined by single-crystal X-ray diffraction analysis. It possesses P212121 space group, with a = 9.9103（5）, b = 13.3597（8）, c = 14.5633（8）A, V= 1928.16（18）A3 ,Mr = 402.30, Z = 4, Dc= 1.386 g/cm^3, 2 = 0.7107A,μ（MoKα）=0.354mm^-1 and F （000） = 840. The structure was refined to R = 0.0280 and wR = 0.0757. In the structure, the pyridine ring adopts a boat conformation.展开更多
1,4-Bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base were synthesized first.Using 1,4- bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base as the monomers,poly(aryl imino) ...1,4-Bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base were synthesized first.Using 1,4- bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base as the monomers,poly(aryl imino) containing acridine units(PAIA) was synthesized via palladium-catalyzed amination.The structure of PAIA was characterized by means of FTIR,~1H-NMR spectroscopy and elemental analysis,the results show an agreement with the proposed structure.The UV absorption and photoluminescence spectra were t...展开更多
The crystal structure N-methyl-9-(4-bromophenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10- decahydroacridine(C20H20BrNO2) was determined by single-crystal X-ray diffraction analysis. It belongs to P21/n space group, with a = ...The crystal structure N-methyl-9-(4-bromophenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10- decahydroacridine(C20H20BrNO2) was determined by single-crystal X-ray diffraction analysis. It belongs to P21/n space group, with a = 10.7999(18), b = 13.845(3), c = 11.4031(3) ?, β = 99.324(4)°, Dc = 1.525 g/cm3, Z = 4, λ = 0.71070 ?, μ(MoKα) = 2.455 mm-1, Mr = 386.28, V = 1682.5(5) ?3, F(000) = 792, the final R = 0.0463 and wR = 0.1053. In the crystal structure, the pyridine ring adopts a boat conformation, the two six-numbered rings fused with pyridine ring adopt twisting boat con- formation.展开更多
The crystal structure of the title compound (C26H33NO4 (C25.68H32.04N0.68O4.32, Mr = 419.35)) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space P21/c with a = 7.519(2), b = ...The crystal structure of the title compound (C26H33NO4 (C25.68H32.04N0.68O4.32, Mr = 419.35)) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space P21/c with a = 7.519(2), b = 28.933(5), c = 10.654(3) ?, β = 91.78(2)°, V = 2316.7(7) ?3, Z = 4, Dc = 1.202 g/cm3, μ = 0.081 mm-1, F(000) = 902, Mr = 423, the final R = 0.0424 and wR = 0.0911. In the structure, the pyridine ring adopts a boat conformation.展开更多
In this work, noncovalent functionalization of multiwalled carbon nanotube （MWNT） with acridine orange （AO） by electropolymerization is studied. The obtained composite film is a viable alternate electrode material...In this work, noncovalent functionalization of multiwalled carbon nanotube （MWNT） with acridine orange （AO） by electropolymerization is studied. The obtained composite film is a viable alternate electrode material, non-toxic, chemical inert, not volatile, using to construct modified electrode. The new type modified electrode has both of unique properties of MWNT and poly acridine orange （POAO）, can provide good sensitivity, low limits of detection, good response precision, and superb response stability.展开更多
Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgi...Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgical interventions sometimes have severe complications due to the status of the original cancers. To avoid the decreased quality of life caused by bone metastasis, minimally invasive surgery that avoids additional surgical morbidity is required. We have established two therapeutic treatments for bone metastasis, a photodynamic acridine orange treatment (AOT) and an electronic magnetic hyperthermia treatment (EMHT). The present study investigated the clinical outcomes of combination therapy with EMHT and AOT for patients with bone metastases in their extremities. Methods: The study included 6 patients with 7 bone cancer metastasis locations. For bone metastases, all patients received intraregional tumor excision supported by AOT, in which photodynamic and radiodynamic therapy kills tumor cells during surgery with minimal damage to normal tissues. After the curettage, bone reconstruction was performed by using magnetic materials with calcium phosphate cement. EMHT was repeatedly performed after surgery. In EMHT, tumor cells are killed with an electric magnetic field generator, and bony union is promoted by electronic stimulation. Results: The mean duration of follow-up was 14 months. During the follow-up period, only one patient experienced a local recurrence, and this recurrence occurred 14 months after surgery. Bony union occurred in 4 of 5 cases (80%), and the pain score was significantly reduced after surgery. Conclusions: In the present study, AOT reduced the invasiveness of surgery. EMHT reduced the tumor growth without major complications and promoted bone formation after surgery. Our clinical results confirmed that EMHT and AOT combination therapy for bone metastasis can preserve limb function without local recurrence or bone absorption.展开更多
A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelect...A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.展开更多
基金the grants from the National Natural Science Foundation of China (81402776 and 81202400)the Key National S&T Progra m "Major New Drug Development" of the Ministry of Science and Technology of China (2012ZX09504001-003)+2 种基金the Fundamental Research Funds for the Central Universities (lzujbky-2014-142 and lzujbky-2015-169)the Specialized Research Fund for the Doctoral Program of Higher Education of China (20130211130005)China Postdoctoral Science Foundation (2013T60896)
文摘The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Ac r_3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence(NLS), a short cationic peptide. To further improve the antimicrobial activity of our agent, dimeric(Acr_3-NLS)_2 was simultaneously synthesized by joining two monomeric Acr_3-NLS together via a disulfide linker. Our results show that Acr_3-NLS and especially(Acr_3-NLS)_2 display signifi cant antimicrobial activity against gramnegative and gram-positive bacteria compared to that of the NLS. Subsequently, the results derived from the study on the mechanism of action demonstrate that Acr_3-NLS and(Acr_3-NLS)_2 can kill bacteria by membrane disruption and DNA binding. The double targets—cell membrane and intracellular DNA—will reduce the risk of bacteria developing resistance to Acr_3-NLS and(Acr_3-NLS)_2. Overall, this study provides a novel strategy to design highly eff ective antimicrobial agents with a dual mode of action for infection treatment.
基金supported by the National Natural Science Foundation of China(No.51972095).
文摘Zirconia nanotube array films(ZNAF)prepared by anodic oxidation method were used as immobilization materials for acridine orange(AO),rhodamine B(RB)and AO-RB systems.A comparative study on their fluorescence emission intensity,fluorescence resonance energy transfer(FRET)and fluorescence detection of nitrite in aqueous solutions and on immobilization films with ZNAF as carriers was carried out.Results demonstrate that the solution pH values and immobilization on ZNAF have a great influence on the per-formance of these fluorescent molecules.Compared with aqueous solutions,the fluorescence emission in-tensity of AO and RB is considerably increased by immobilization,which is 8.0 and 4.2 times higher than the original,respectively.The energy transfer efficiency(E)of the AO-RB system increases from 40.9%to 84.8%by loading it on ZNAF.Moreover,after immobilization onto ZNAF,the fluorescence detection performance of nitrite is also significantly improved.The limit of detection decreases from 0.95 ng/mL to 0.22 ng/mL and the sensitivity increases from 939.18 to 15,031.68 mL/μg through loading AO onto ZNAF.
基金Peking University Comprehensive Platform for Innovative Drug Research and Development(Grant No.2009ZX--09301--010)
文摘We have developed an on-line detection method using acridine orange as the fluorescence probe and applied this method to rapidly identify active compounds in herbal medicines. This on-line method was equipped with a high-performance liquid chromatography tandem diode array detector, electrospray ionization-ion-trap time-of-flight mass spectrometry and DNA- acridine orange fluorescence detection （HPLC-DAD-MSn-DNA-AO-FLD）. A large amount of information could be simultaneously obtained during one run, which included HPLC fingerprint, ultraviolet spectra, total ion chromatograms, MSn data of high-resolution mass spectrometry and activity profile of each compound binding with DNA. The method also provided information on structureactivity relationships and mechanism of interaction. We used this on-line method to identify five DNA-binding activity components from Lithospermum erythrorhizon sample for the first time. The result showed that the parent nucleus of shikonin derivatives could bind with DNA. The structure-activity relationship showed that the parent nucleus of shikonin derivatives plays a major role in DNA binding, not the carboxyl group on the side chain. This simple, rapid, high precision and good stability on-line method should be useful for compound separation, structural identification and screening of DNA-binding compounds in herbal medicines.
基金financial supports from the Shenzhen Development and Reform Committee(Nos.20151961 and 2019156)Department of Science and Technology of Guangdong Province(No.2017B030314083)。
文摘In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation.In addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory activities.Subsequent mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells.Our study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.
基金This project is financially supported by the Natural Science Foundation of China (QT program)
文摘A new photocatalyst, TiO_2 powder immobilized on polystyrene (PS) thin films,was prepared using a novel method and its photocatalytic activity on the photodegradation ofacridine dye in aqueous solution was tested. By this method, the crystal form and grain size of theimmobilized TiO_2 were well maintained. Compared with TiO_2 powder, the photocatalytic activity ofTiO_2/PS thin films was not significantly reduced. The catalyst is stable and can be reused severaltimes without the loss of activity, which makes wastewater treatment using this photocatalyticdegradation technique of this way possible in the practical application.
基金the financial support from the National Natural Science Foundation of China(Nos.21473164,21603195 and 21875225)Major project of Technical Innovation of Hubei Province(No.2017AAA126)the Fundamental Research Funds for Central Universities,China University of Geosciences(Wuhan)(Nos.CUGL170405 and CUG180604)。
文摘Hydrogen has been deemed as one of the most efficient energy carriers for a broad variety of industrial applications[1,2].Large-scale,low-cost hydrogen production,safe storage and delivery represent a tremendous technological challenge and have become a subject of intense research and development activities in the past few decades[3–5].
基金the financial support from the National Natural Science Foundation of China(Nos.21072040,21071040, 21101051 and 21272050)the Program for New Century Excellent Talents in University of the Chinese Ministry of Education(No.NCET-11-0627)
文摘Graphene/acridine （G-Acr） hybrid structures were synthesized through covalent functionalization of graphene oxide with 9-（4- aminophenyl）acridine （APA） and its derivatives. The G-Act hybrids were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, thermal gravimetric analysis and Raman spectroscopy. X-ray photoelectron spectroscopy confirms that the binding energies of APA and its derivatives shifted to higher values, revealing pronounced charge transfer at the interface of graphene and organic molecules.
基金supported by grants from the Scientific Support Project of Anhui Province Education Department of China (Grant No. KJ2012ZD08 and KJ2012Z162)the National Scientific and Technological Support Projects of China (Grant No. 81101273)the National Natural Science Foundation of China (Grant No. 30872253)
文摘Objeαive： To determine whether Interferon-alpha-2b （IFN-α2b） can modulate the autophagic response in hepatocellular carcinoma cells. Methods： Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission eleαron microscopy and immunoblotting. Results： Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. The acridine orange HepG2 cell ratios were （4.3±1.0）%, （6.9±1.4）%, and （13.1±2.3）%, respeαively, after treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punαate pattern was observed in HepG2 cells treated with 10,000 IU/mL [FN-α2b for 48 h, but only diffuse and weakly fluorescent GFP-LC3 punαa was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like charaαeristics, including single- or double-membrane vacuoles containing intaα and degraded cellular debris. The Beclinl and LC3-II protein expression was up-regulated by IFN-α2b treatment. Conclusion： Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclinl signaling pathway was stimulated by IFN-α2b.
基金supports from the Ministry of Science and Technology of China(Nos. 2012ZX09506001-010,2012AA020305 and 2011DFA30620)the National Natural Science Foundation of China(Nos.21272134 and 20902053)Shenzhen Sci & Tech Bureau(No. JCYJ20120831165730905)
文摘Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues,LXL 1-5,were synthesized and their antiproliferative activity against HepC-2 cell lines were evaluated,among which the 9-benzyloxyacridine analogue,LXL-5, showed inhibitory activity against tyrosine kinases,VEGFR-2 and Src.The results of UV-visible absorption spectra and fluorescence emission spectra,as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity.Our study suggested that acridine scaffold,previously shown to have no multi-target kinase and topoisomerase inhibitory activity,might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.
基金the Ministry of Science and Technology of the People’s Republic of China(Nos.2012AA020305and 2011DFA30620)the National Natural Science Foundation of China(Nos.21272134 and 21372141)Shenzhen Sci.&Tech.Bureau(No.JCYJ20120831165730905)for the financial supports
文摘Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.
基金supported by a grant from STCSM (Subject No.:074207002)
文摘Objective To estimate the predictive value of double fluorescence [acridine orange （AO）/propidium iodide （PI）] staining results for fertilization rate and clinical outcomes and analyze the correlation between the results of AO/P1 staining and sperm apoptosis. Methods A prospective study was carried out, 235 infertile couples remedied using traditional in vitro fertilization （IVF） were included. Semen collected from 235 patients were stained by fluorescence dye, AO and PL at the same time the spermatozoa apoptosis rate was calculated by using flow cytometry to detect the rate of Annexin V＋/ PI- . The result of fluorescence was divided into 3 groups as green （G）, yellow （Y） and red （R） according to the color of fluorescence. The correlation between the percent of the 3 colors and clinical outcomes and spermatozoa apoptosis rate was evaluated. Results Significant negative correlation was observed between the percentage of Y and fertilization rate （r= -0.42, P=0.04）, no significant correlation was observed between the percentage of G, R and fertilization rate. The percentage of G, Y, R was not significantly different between pregnant patients and non-pregnant patients, respectiw,ly, while the percentage of Y was significant different between miscarriage patients and liveborn patients （r=0.6L P=0.01） and no significant difference exist in the percentage of G and R between liveborn patients and miscarriage patients. There was a significant positive correlation between the percentage of Y and the rate of Annexin V＋/ PI （r=0.53, P=0.04）, and no significant correlation was shown between the percentage of G, R and the rate of Annexin V＋/ PI-.Conclusion The percentage of yellow group of double fluorescence （AO/PI） staining will affect the fertilization rate and the miscarriage rate, and this group of spermatozoa may be connected with the spermatozoa apoptosis.
基金supported by the grant(No.852)from Pasteur Institute of Iran to A.A.Mehrizi
文摘Objective:To evaluate new compounds synthesized by integrating quinoline,quinazoline,and acridine rings with the active moiety of(5-nitroheteroaryl)methylene hydrazine.Methods:A new series of compounds(1a,1b,2a,2b,3a,and 3b)were synthesized and evaluated for cytotoxicity against COS-7 cells using the MTT assay.In vitro anti-plasmodial activity of the compounds was measured against CQ-sensitive(3D7)and CQ-resistant(K1)Plasmodium(P.)falciparum strains.β-hematin assay was performed to assess the inhibitory effects ofβ-hematin formation for new compounds.Results:The synthetic compounds had anti-plasmodial activity against blood-stage of 3D7[IC50=(0.328-5.483)μM]and K1[IC50=(0.622-7.746)μM]strains of P.falciparum,with no cytotoxicity against COS-7 cells in effective doses.Compounds 1a,1b,and 2b were the most effective derivatives against P.falciparum 3D7 and K1 strains.Based on theβ-hematin assay,the inhibition ofβ-hematin formation is the main mechanism of the inhibitory effect of these compounds.Conclusions:The synthetic compounds could inhibit the erythrocytic stages of CQ-sensitive and resistant P.falciparum strains without toxicity towards mammalian cells.Compounds 1b,2a,and 2b had comparable anti-plasmodial activity against both CQ-sensitive(3D7)and resistant(K1)P.falciparum strains.These compounds may be promising lead structures for the development of new anti-malarial drugs.
基金Supported by the National Natural Science Foundation of China(No.20672091)
文摘Under microwave irradiation, the one-pot multicomponent condensation reaction of three moles of aromatic aldehydes with two moles of cyclic ketones having free a,a＇-methylene positions such as cyclopentanone or cyclohexanone in the presence of ammonium acetate and acetic acid afforded dicycloalkenopyridines with two a-arylidene groups in high yields. Under the similar reaction condition, the reaction of aromatic aldehydes with 1-tetralone having only one a-methylene position alternatively resulted in 10-aryl-2,3：5,6-dibenzoacridines.
基金This work was supported by the National Natural Science Foundation of China (No. 20372057), the Natural Science Foundation of the Jiangsu Province (No. BK2001142), the Suzhou University Organic Syntheses Open Laboratory of Jiangsu Province (No. S8109111) and the Key Lab of Biotechnology for Medicinal Plants of Jiangsu Province (No. 01AXL 14)
文摘The N-cyclopropyl-9-（3,4-dicholophenyl）- 1,2,3,4,5,6,7,8,9,10-decahydroacri- dine-1,8-dione was synthesized by the reaction of 1,3-cyclohexanedione, N-cyclopropylamine and 3,4-dicholoaldehyde in water and glycol under microwave irradiation. Its crystal structure was determined by single-crystal X-ray diffraction analysis. It possesses P212121 space group, with a = 9.9103（5）, b = 13.3597（8）, c = 14.5633（8）A, V= 1928.16（18）A3 ,Mr = 402.30, Z = 4, Dc= 1.386 g/cm^3, 2 = 0.7107A,μ（MoKα）=0.354mm^-1 and F （000） = 840. The structure was refined to R = 0.0280 and wR = 0.0757. In the structure, the pyridine ring adopts a boat conformation.
基金supported by the Foundation of National Key Laboratory of High Temperature and Density Plasma Physics(No.9140C6806030807)the Science and Technology Development Foundation of China Academy of Physics Engineering(No.200708006)
文摘1,4-Bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base were synthesized first.Using 1,4- bis-(4-bromobenzoyl)benzene and proflavine,3,6-diaminoacridine free base as the monomers,poly(aryl imino) containing acridine units(PAIA) was synthesized via palladium-catalyzed amination.The structure of PAIA was characterized by means of FTIR,~1H-NMR spectroscopy and elemental analysis,the results show an agreement with the proposed structure.The UV absorption and photoluminescence spectra were t...
基金This work was supported by the National Natural Science Foundation of China (No. 20372057) Natural Science Foundation of Jiangsu Province (No. BK2001142) the Suzhou University Organic Synthesis Open Laboratory of Jiangsu Province (No. S81091 11) and the Key Lab of Biotechnology for Medicinal Plants of Jiangsu Province (No. 01AXL 14)
文摘The crystal structure N-methyl-9-(4-bromophenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10- decahydroacridine(C20H20BrNO2) was determined by single-crystal X-ray diffraction analysis. It belongs to P21/n space group, with a = 10.7999(18), b = 13.845(3), c = 11.4031(3) ?, β = 99.324(4)°, Dc = 1.525 g/cm3, Z = 4, λ = 0.71070 ?, μ(MoKα) = 2.455 mm-1, Mr = 386.28, V = 1682.5(5) ?3, F(000) = 792, the final R = 0.0463 and wR = 0.1053. In the crystal structure, the pyridine ring adopts a boat conformation, the two six-numbered rings fused with pyridine ring adopt twisting boat con- formation.
基金The project was supported by the National Natural Science Foundation of China (No. 20372057) Natural Science Foundation+4 种基金 of Jiangsu Province (No. BK.2001142) the Open-end Fund of the Key Experiments of Organic Synthesis Jiangsu Province (S8109111) the Fund of Jiangsu Provincial Key Lab of Biotechnology for Medicinal Plants (01AXL 14)
文摘The crystal structure of the title compound (C26H33NO4 (C25.68H32.04N0.68O4.32, Mr = 419.35)) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space P21/c with a = 7.519(2), b = 28.933(5), c = 10.654(3) ?, β = 91.78(2)°, V = 2316.7(7) ?3, Z = 4, Dc = 1.202 g/cm3, μ = 0.081 mm-1, F(000) = 902, Mr = 423, the final R = 0.0424 and wR = 0.0911. In the structure, the pyridine ring adopts a boat conformation.
文摘In this work, noncovalent functionalization of multiwalled carbon nanotube （MWNT） with acridine orange （AO） by electropolymerization is studied. The obtained composite film is a viable alternate electrode material, non-toxic, chemical inert, not volatile, using to construct modified electrode. The new type modified electrode has both of unique properties of MWNT and poly acridine orange （POAO）, can provide good sensitivity, low limits of detection, good response precision, and superb response stability.
文摘Cancer patients with bone metastases in their extremities may require surgical intervention to prevent deterioration in their quality of life due to a pathological fracture or severe bone pain. However, curative surgical interventions sometimes have severe complications due to the status of the original cancers. To avoid the decreased quality of life caused by bone metastasis, minimally invasive surgery that avoids additional surgical morbidity is required. We have established two therapeutic treatments for bone metastasis, a photodynamic acridine orange treatment (AOT) and an electronic magnetic hyperthermia treatment (EMHT). The present study investigated the clinical outcomes of combination therapy with EMHT and AOT for patients with bone metastases in their extremities. Methods: The study included 6 patients with 7 bone cancer metastasis locations. For bone metastases, all patients received intraregional tumor excision supported by AOT, in which photodynamic and radiodynamic therapy kills tumor cells during surgery with minimal damage to normal tissues. After the curettage, bone reconstruction was performed by using magnetic materials with calcium phosphate cement. EMHT was repeatedly performed after surgery. In EMHT, tumor cells are killed with an electric magnetic field generator, and bony union is promoted by electronic stimulation. Results: The mean duration of follow-up was 14 months. During the follow-up period, only one patient experienced a local recurrence, and this recurrence occurred 14 months after surgery. Bony union occurred in 4 of 5 cases (80%), and the pain score was significantly reduced after surgery. Conclusions: In the present study, AOT reduced the invasiveness of surgery. EMHT reduced the tumor growth without major complications and promoted bone formation after surgery. Our clinical results confirmed that EMHT and AOT combination therapy for bone metastasis can preserve limb function without local recurrence or bone absorption.
基金Funded by the National Natural Science Foundation of China(Nos.50802069,81100890,51272191)the Fundamental Research Funds for the Central Unversities(WUT:2013-IV-010)the Students Innovation and Entrepreneurship Training Program of WHUT(20141049701012)
文摘A novel fluorescent probe 9-（4-（1,2-diamine）benzene-N1-phenyl）acridine（DABPA） was synthesized for the detection of nitric oxide（NO） and characterized by IR, 1H-NMR and EI-MS spectroscopy. Based on a photoelectron transfer mechanism, the fl uorescence intensities of DABPA were investigated with the different concentrations of NO. Under the optimal experimental conditions, the fl uorescence intensity of DABPA had a good linear relationship（R2=0.9977） with NO concentration in the range from 1×10-7 to 1.5×10-6 mol/L with a detection limit of 1×10-8 mol/L. The cytotoxicity induced by DABPA was evaluated by the MTT（3-（4,5-dimethylthiazol-2-yl）-2,5diphenyl tetrazolium bromide） assay for biological application. Furthermore, the probe DABPA had also been successfully applied to real-time image NO produced in PC12 cells in the presence of L-arginine.
