Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide

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.

Photocatalytic performance of TiO_2 immobilized on polystyrene (PS) thin film for mineralization of pollutants

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.

Fast hydrogenation kinetics of acridine as a candidate of liquid organic hydrogen carrier family with high capacity

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].

Interferon-alpha-2b induces autophagy in hepatocellular carcinoma cells through Beclin1 pathway

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.

In vitro anti-plasmodial activity of new synthetic derivatives of 1-(heteroaryl)-2-((5-nitroheteroaryl)methylene) hydrazine

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.

Efficient Synthesis of Dicycloalkenopyridines:One-pot Multicomponent Condensation of Aldehydes with Cyclic Ketones

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.

Synthesis and Crystal Structure of N-cyclopropyl-9 -(3,4-dicholophenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine -1,8-dione under Microwave Irradiation

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.

SYNTHESIS AND PHOTOPHYSICAL PROPERTIES OF POLY(ARYL IMINO)CONTAINING ACRIDINE UNITS(PAIA)

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...

Synthesis and Crystal Structure of N-methyl-9-(4-bromophenyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione under Microwave Irradiation

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.

Synthesis and Crystal Structure of N-Methyl-9-(3,4-dimethoxylphenyl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10- decahydroacridine under Microwave Irradiation

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.

Electrocatalytic behaviors of poly acridine orange/multi-walled carbon nanotube modified electrode

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.

A Minimally Invasive Surgery for Bone Metastases Using the Combination of Photodynamic Therapy and Hyperthermia Treatment

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.

A Novel Fluorescence Probe 9-(4-(1,2-diamine)benzeneN^1-phenyl)acridine for Nitric Oxide Determination

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.

Studies on Photocatalytic Degradation of Acridine Orange and Chloroform Sensing Using As-Grown Antimony oxide Microstructures

Flower shaped antimony oxide (Sb2O3) microstructures were synthesized in a large quantity via simple solution method using aqueous mixtures of antimony chloride and hexamethylene diamine (HMDA). The morphological characterizations were done by field emission scanning electron microscopy (FESEM), which revealed that the synthesized products possess flower-shaped microstructures. The detailed structural characterizations performed by X-ray diffraction (XRD), Fourier transform infrared spectrophotometer (FT-IR) and Raman spectrophotometer confirmed that the synthesized microstructures are well-crystalline antimony oxide. The Energy dispersive spectroscopy (EDS) shows that the grown products are composed of Sb and O. Optical properties of the synthesized products were characterized by UV-Visible spectrophotometer which exhibits a well defined peak at ~ 291.0 nm. The photo-catalytic activity of the Sb2O3 microstructures was evaluated by degradation of acridine orange (AO), which mineralized almost 63.0% in 150 min. The chemical sensing properties of Sb2O3 microstructures was also studied by I-V technique using chloroform as a detecting solvent. The fabricated chloroform sensor demonstrates good sensitivity of 0.1154 μA cm–2 mM–1, lower-detection limit (~0.1 mM), large-linear dynamic range (LDR, 0.122 mM to 1.22 M) with linearity (R = 0.7898) in short response time (10.0 sec).

A Method for Determination of Critical Micellar Concentration of Surfactant

Measure the chemiluminescence value of acridine compound as luminescent agent in the surfactant solution with a series of concentrations,according to the value of the obtained luminescent value and the value of the corresponding surfactant concentration in the surfactant solution,linear fitting is carried out to obtain several fitting lines,and the minimum value of the surfactant concentration corresponding to the intersection of the two adjacent fitting lines is the critical micelle concentration of the surfactant.According to the results,the critical micelle concentration of Dodecyl trimethyl ammonium chloride is 11.5 mmol/L,Hexadecyl trimethyl ammonium Bromide is 0.357 mmol/L,Sodium dodecyl sulfate is 7.64 mmol/L,sodium N-lauroylsarcosinate is 0.890 mmol/L,Triton X-100 is 0.309 mmol/L,3-((3-Cholamidopropyl)dimethylammonium)-1-propanesulfonate is 9.53 mmol/L,3-(N,N-dimethyldodecylammonio)propanesulfonate is 1.73 mmol/L.The results were similar to those obtained by traditional methods,the method can be used in the study of critical micelle concentration of surfactants.

Fluoresence quenching method for the determintion of trace amount of cadmium with iodide-acridine red system

Ａｎｕｍｂｅｒｏｆｆｌｕｏｒｅｓｃｅｎｃｅｍｅｔｈｏｄｓｈａｖｅｂｅｅｎｒｅｐｏｒｔｅｄｆｏｒｔｈｅｄｅｔｅｒｍｉｎａｔｉｏｎｏｆｃａｄｍｉｕｍ，ｂａｓｅｄｏｎｉｔｓｃｏｍｐｌｅｘｗｉｔｈｏｒｇａｎｉｃｄｙｅｓ，ｓｕｃｈａｓ８ｈｙｄｒｏｘｙｑｕｉｎ...

On-line HPLC-DAD coupled with ESI-IT-TOF-MS and fluorescence detection to identify DNA-binding compounds from Lithospermum erythrorhizon using acridine orange as the fluorescence probe

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.

Combination and cleavage of HBV DNA fragments by triple helix-forming oligonucleotides modified with manganese porphyrin in vitro

Objective To observe the ability of triple helix-forming oligonucleotides (TFOs) modified with manganese porphyrin to combine with and cleave HBV DNA fractions. Methods TFO were modified with manganese porphyrin and acridines,and then reacted with the 32 P labeled HBV DNA fragments at 37℃ in vitro (pH 7.4). Electrophoretic mobility shift assays and DNase Ⅰ footprinting tests were used to show the affinity and specificity of TFO to bind to target sequences. The ability of TFO to cleave HBV DNA fragments was tested by cleavage experiments. Results TFO modified with manganese porphyrin and acridine could bind to the target sequence in a sequence-dependent manner,with a Kd value of 3.5×10 -7 mol/L and a relative affinity of 0.008. In the presence of potassium monopersulfate (KHSO 5),TFO modified with manganese porphyrin and acridine could cleave the target sequence where the triplex DNA was formed. Conclusion In the presence of KHSO 5,TFO modified with manganese porphyrin and acridine could bind and cleave the target HBV-DNA in a sequence-dependent manner.

Design,synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents

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.

Fluorescence enhancement of acridine orange in a water solution by Au nanoparticles

The surface enhanced fluorescence effect of acridine orange fluorophore in the proximity of Au nanoparticles has been investigated experimentally in the system of aqueous solution.Significant enhancement of the fluorescence intensity was observed when the system was excited with 532 nm or 442 nm CW lasers.The influence of the distances between neighboring Au particles as well as that between the fluorophore molecules and the Au surface were explored experimentally.The results demonstrated that a compact distribution of metallic particles was able to produce stronger fluorescence enhancement.Proper separation between the fluorophore molecules and the metal surface was favorable for a better enhancement.