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Journal of Chromatographic Science Apr 2016Two sensitive and selective analytical methods were developed for simultaneous determination of aminoacridine hydrochloride and lidocaine hydrochloride in bulk powder...
Two sensitive and selective analytical methods were developed for simultaneous determination of aminoacridine hydrochloride and lidocaine hydrochloride in bulk powder and pharmaceutical formulation. Method A was based on HPLC separation of the cited drugs with determination of the toxic lidocaine-related impurity 2,6-dimethylaniline. The separation was achieved using reversed-phase column C18, 250 × 4.6 mm, 5 µm particle size and mobile phase consisting of 0.05 M disodium hydrogen phosphate dihydrate (pH 6.0 ± 0.2 adjusted with phosphoric acid) and acetonitrile (55 : 45, v/v). Quantitation was achieved with UV detection at 240 nm. Linear calibration curve was in the range of 1.00-10.00, 13.20-132.00 and 1.32-13.20 µg mL(-1) for aminoacridine hydrochloride, lidocaine hydrochloride and 2,6-dimethylaniline, respectively. Method B was based on TLC separation of the cited drugs followed by densitometric measurement at 365 nm on the fluorescent mode for aminoacridine hydrochloride and 220 nm on the absorption mode for lidocaine hydrochloride. The separation was carried out using ethyl acetate-methanol-acetic acid (65 : 30 : 5 by volume) as a developing system. The calibration curve was in the range of 25.00-250.00 ng spot(-1) and 0.99-9.90 µg spot(-1) for aminoacridine hydrochloride and lidocaine hydrochloride, respectively. The results obtained were statistically analyzed and compared with those obtained by applying the manufacturer's method.
Topics: Administration, Oral; Aminacrine; Chromatography, High Pressure Liquid; Drug Contamination; Gels; Lidocaine; Pharmaceutical Preparations
PubMed: 26671412
DOI: 10.1093/chromsci/bmv170 -
American Journal of Alzheimer's Disease... May 2016In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides...
In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer's disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer's disease.
Topics: Alzheimer Disease; Aminacrine; Cholinesterase Inhibitors; Humans; In Vitro Techniques
PubMed: 26385945
DOI: 10.1177/1533317515603115 -
Journal of Neurochemistry Mar 2015Previous works have shown the interest of naturally fluorescent proflavine derivatives to label Abeta deposits in vitro. This study aimed to further characterize the...
Previous works have shown the interest of naturally fluorescent proflavine derivatives to label Abeta deposits in vitro. This study aimed to further characterize the properties of the proflavine 3-acetylamino-6-[3-(propargylamino)propanoyl]aminoacridine (COB231) derivative as a probe. This compound was therefore evaluated on human post-mortem and mice brain slices and in vivo in 18-month-old triple transgenic mice APPswe, PS1M146V and tauP301L (3xTgAD) mice presenting the main characteristics of Alzheimer's disease (AD). COB231 labelled amyloid plaques on brain slices of AD patients, and 3xTgAD mice at 10 and 0.1 μM respectively. However, no labelling of the neurofibrillary tangle-rich areas was observed either at high concentration or in the brain of fronto-temporal dementia patients. The specificity of this mapping was attested in mice using Thioflavin S and IMPY as positive controls of amyloid deposits. After intravenous injection of COB231 in old 3xTgAD mice, fluorescent amyloid plaques were detected in the cortex and hippocampus, demonstrating COB231 blood–brain barrier permeability. We also controlled the cellular localization of COB231 on primary neuronal cultures and showed that COB231 accumulates into the cytoplasm and not into the nucleus. Finally, using a viability assay, we only detected a slight cytotoxic effect of COB231 (< 10%) for the highest concentration (100 μM).
Topics: Alzheimer Disease; Aminacrine; Animals; Autopsy; Brain; Disease Models, Animal; Female; Fluorescent Dyes; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Plaque, Amyloid; Proflavine; Sensitivity and Specificity; Staining and Labeling
PubMed: 25258048
DOI: 10.1111/jnc.12951 -
Retrovirology Jun 2014Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of CD4+CD25+ lymphocytes caused by human T-cell lymphotropic virus type 1. While much progress has been...
BACKGROUND
Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of CD4+CD25+ lymphocytes caused by human T-cell lymphotropic virus type 1. While much progress has been made in understanding the mechanisms of cellular dysregulation, the prognosis for aggressive ATL still remains poor. Therefore, new therapeutic approaches need to be developed.
RESULTS
Previously, we demonstrated that the viral protein Tax inactivates p53 in HTLV-1-infected T-cells. Here we show that 9-aminoacridine (9AA) through p53 reactivation and NF-κB inhibition has selective toxicity for infected leukemic cells independent of their p53 status. We further demonstrate that 9AA activates caspase-3/7 resulting in PARP cleavage. Next we investigated the efficacy of 9AA in the MET-1 ATL model. Alone, 9AA did not cause significant drops in surrogate tumor markers, soluble IL-2Rα or β2-micorglobulin (β2μ) levels with only a slight increase in survival of MET-1-bearing mice. However, in combination with Campath-1H, 9AA treatment resulted in low soluble IL-2Rα and β2μ levels at 2 and 4 weeks. Consistent with reduced tumor cell burden, combination treatment significantly increased survival of MET-1-bearing mice compared to mice treated with either drug alone. Splenic cells isolated from 9AA or combination treated mice showed increased p53 protein levels and transcriptional activity. Consistent with increased tumor suppressor activity, we found increased PARP-1 cleavage in 9AA and combination treated cells.
CONCLUSION
Our results indicate that targeting reactivation of p53 and inhibition of NF-κB with acridine-derivatives in combination with other chemotherapeutics could result in increased efficacy and selective killing of tumor cells.
Topics: Alemtuzumab; Aminacrine; Animals; Antibodies, Monoclonal, Humanized; Caspase 3; Caspase 7; Cell Line, Tumor; Disease Models, Animal; Humans; Interleukin-2 Receptor alpha Subunit; Jurkat Cells; Leukemia-Lymphoma, Adult T-Cell; Mice; Mice, Inbred NOD; Mice, SCID; NF-kappa B; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; T-Lymphocytes; Transcription, Genetic; Tumor Suppressor Protein p53
PubMed: 24890041
DOI: 10.1186/1742-4690-11-43 -
Cellular & Molecular Biology Letters Mar 2014The recently described method of cell electroporation by flow of cell suspension through localized direct current electric fields (dcEFs) was applied to identify...
The recently described method of cell electroporation by flow of cell suspension through localized direct current electric fields (dcEFs) was applied to identify non-toxic substances that could sensitize cells to external electric fields. We found that local cationic anesthetics such as procaine, lidocaine and tetracaine greatly facilitated the electroporation of AT2 rat prostate carcinoma cells and human skin fibroblasts (HSF). This manifested as a 50% reduction in the strength of the electric field required to induce cell death by irreversible electroporation or to introduce fluorescent dyes such as calcein, carboxyfluorescein or Lucifer yellow into the cells. A similar decrease in the electric field thresholds for irreversible and reversible cell electroporation was observed when the cells were exposed to the electric field in the presence of the non-toxic cationic dyes 9-aminoacridine (9-AAA) or toluidine blue. Identifying non-toxic, reversibly acting cell sensitizers may facilitate cancer tissue ablation and help introduce therapeutic or diagnostic substances into the cells and tissues.
Topics: Aminacrine; Anesthetics; Animals; Cations; Cell Line, Tumor; Electricity; Electroporation; Fibroblasts; Fluoresceins; Humans; Rats; Surface Properties
PubMed: 24415057
DOI: 10.2478/s11658-013-0114-z -
Genes To Cells : Devoted To Molecular &... Nov 2013Cell-in-cell structures represent live cell events in which one cell internalizes another. Because formation of cell-in-cell structures is a rare event in most cell...
Cell-in-cell structures represent live cell events in which one cell internalizes another. Because formation of cell-in-cell structures is a rare event in most cell types and the event is associated with cell death, there has been limited clarification of this phenomenon, and its physiological role and molecular mechanism are yet to be precisely elucidated. In this study, we established a mutagenized cell line that exhibited cell-in-cell structures at a more than 10-fold higher frequency as compared to the parent cells. Interestingly, both engulfment and invasion were increased in the mutagenized cell line as compared with that in the parent cell line in the suspension culture condition. This finding indicates that this mutagenized cell line showed an interchangeable status in terms of its ability to form cell-in-cell structures, and the system described here could be useful for elucidation of the mechanisms regulating the formation of cell-in-cell structures, including engulfment and invasion, in a given cellular environment. Further studies using this cell line are warranted to understand the mechanism of formation and biological significance of the cell-in-cell formation.
Topics: Aminacrine; Cell-in-Cell Formation; HCT116 Cells; Humans; Mutagenesis; Mutation Rate; Nitrogen Mustard Compounds; Phenotype
PubMed: 24165024
DOI: 10.1111/gtc.12092 -
Organic & Biomolecular Chemistry Jun 2013On deprotonation, 1-arylindazolium salts form 1-arylindazol-3-ylidenes which rearrange spontaneously via ring cleavage, ring closure and subsequent proton transfer to...
On deprotonation, 1-arylindazolium salts form 1-arylindazol-3-ylidenes which rearrange spontaneously via ring cleavage, ring closure and subsequent proton transfer to substituted 9-aminoacridines. By contrast, the N-heterocyclic carbene of 2-phenylindazolium cannot rearrange similarly and was trapped by sulfur.
Topics: Aminacrine; Cyclization; Indazoles; Methane; Molecular Structure; Palladium
PubMed: 23613125
DOI: 10.1039/c3ob40379c -
Methods in Molecular Biology (Clifton,... 2013Capillary electrophoresis is a common technique used for glycosaminoglycan-derived disaccharide analysis because of its high resolving power, high separation efficiency,...
Capillary electrophoresis is a common technique used for glycosaminoglycan-derived disaccharide analysis because of its high resolving power, high separation efficiency, high sensitivity, short analysis time, and straightforward operation. CE coupled to laser-induced fluorescence (LIF) detection shows an approximately 100 times higher sensitivity than traditional UV detection at 232 nm. 2-Aminoacridone (AMAC) is a widely used fluorophore for labeling unsaturated disaccharides by deductive amination, which is one of the most important method of derivatization of disaccharides for CE-LIF detection. Outlined in this chapter is a protocol of analyzing glycosaminoglycan-derived disaccharides by CE-LIF with AMAC derivatization.
Topics: Aminacrine; Calibration; Carbohydrate Conformation; Carbohydrate Sequence; Disaccharides; Electrophoresis, Capillary; Glycosaminoglycans; Reference Standards
PubMed: 23386338
DOI: 10.1007/978-1-62703-296-4_7 -
American Journal of Physiology. Cell... Oct 2011The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. The F508del defect can be partially overcome at low...
The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. The F508del defect can be partially overcome at low temperature (27°C) or with pharmacological correctors. However, the efficacy of correctors on the mutant protein appears to be dependent on the cell expression system. We have used a bronchial epithelial cell line, CFBE41o-, to determine the efficacy of various known treatments and to discover new correctors. Compared with other cell types, CFBE41o- shows the largest response to low temperature and the lowest one to correctors such as corr-4a and VRT-325. A screening of a small-molecule library identified 9-aminoacridine and ciclopirox, which were significantly more effective than corr-4a and VRT-325. Analysis with microarrays revealed that 9-aminoacridine, ciclopirox, and low temperature, in contrast to corr-4a, cause a profound change in cell transcriptome. These data suggest that 9-aminoacridine and ciclopirox act on F508del-CFTR maturation as proteostasis regulators, a mechanism already proposed for the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). However, we found that 9-aminoacridine, ciclopirox, and SAHA, in contrast to corr-4a, VRT-325, and low temperature, do not increase chloride secretion in primary bronchial epithelial cells from CF patients. These conflicting data appeared to be correlated with different gene expression signatures generated by these treatments in the cell line and in primary bronchial epithelial cells. Our results suggest that F508del-CFTR correctors acting by altering the cell transcriptome may be particularly active in heterologous expression systems but markedly less effective in native epithelial cells.
Topics: Aminacrine; Bacterial Proteins; Benzamides; Cell Line; Cell Membrane; Chlorides; Ciclopirox; Cold Temperature; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation; Humans; Hydroxamic Acids; Luminescent Proteins; Mutation; Piperazines; Protein Transport; Pyridones; Quinazolines; Thiazoles; Vorinostat
PubMed: 21753184
DOI: 10.1152/ajpcell.00507.2010 -
Journal of Neurochemistry Dec 2010Polyamine-containing toxins and synthetic dicationic derivatives of adamantane and phenylcyclohexyl selectively antagonize Ca(2+)-permeable... (Comparative Study)
Comparative Study
Polyamine-containing toxins and synthetic dicationic derivatives of adamantane and phenylcyclohexyl selectively antagonize Ca(2+)-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor channels. These compounds demonstrate voltage-dependent open-channel block and are trapped by closed channels. In this study, we describe an alternative mechanism of non-competitive AMPA receptor inhibition caused by 9-aminoacridine and some of its derivatives. These compounds exhibit similar potency against Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors. The inhibition is largely voltage-independent, binding and unbinding do not require presence of agonist. We conclude that 9-aminoacridine binds to a shallow site in the AMPA receptor, which is located above the activation gate. A comparison of three-dimensional structures of the antagonists suggests that the 'V-like' shape of the hydrophobic headgroup favors voltage-dependent binding to the deep site in the channel pore, whereas the compounds possessing flat aromatic headgroups preferably bind to the shallow site. The characterization of the novel mechanism of AMPA receptor channel antagonism opens a way to develop a new family of pharmacological agents, which can be of scientific and practical importance.
Topics: Aminacrine; Animals; Animals, Newborn; Binding Sites; Rats; Rats, Wistar; Receptors, AMPA
PubMed: 20969571
DOI: 10.1111/j.1471-4159.2010.07068.x