- Syntheses and copper(II)-dependent DNA photocleavage by acridine and anthracene 1,10-phenanthroline conjugate systems
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We report the syntheses and characterization of a series of compounds based on 1,10-phenanthroline covalently tethered, at the 2 and 9 positions, to either two benzene, naphthalene, acridine or anthracene chromophores. The acridine and anthracene derivati
- Gude, Lourdes,Fernandez, Maria-Jose,Grant, Kathryn B.,Lorente, Antonio
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- Chlorpromazine metabolism. IV: Quaternization as a key to determination of picomoles of chlorpromazine and other tertiary amine drugs
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Reaction of chlorpromazine with 9 bromomethylacridine under appropriate conditions yields a nonfluorescent quaternary ammonium derivative which, on subsequent photolysis, liberates fluorescence. The major component of this fluorescence is 9 methylacridine (86%), while two minor components are 9 acridine carboxaldehyde (6%) and 9 acridinemethanol (8%). The mechanism of photolysis leading to formation of these products appears to involve homolytic as well as heterolytic cleavages of the quaternary salt. Both quaternization and the photolysis are stoichiometric. Appropriate isolation of the fluorescence and its quantitative determination constitutes the basis of a new and highly sensitive assay applicable to chlorpromazine and other tertiary amine drugs.
- Lehr,Kaul
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- Lattice energetics and thermochemistry of acridine derivatives and substituted acridinium trifluoromethanesulphonates
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The enthalpies and temperatures of melting of eight 9-substituted acridines (alkyl, aryl or alkoxy) (I) and six their 10-methylated-acridinium trifluoromethanesulphonate (II) derivatives were measured by DSC. The enthalpies and temperatures of volatilisation of the first group of compounds were also determined by DSC or obtained by fitting TG curves to the Clausius–Clapeyron relationship. By combining the enthalpies of formation of gaseous acridines or 10-methylacridinium trifluoromethanesulphonate ions, obtained by the DFT method, and the corresponding enthalpies of sublimation and/or crystal lattice enthalpies, the enthalpies of formation of the compounds in the solid phase were predicted. For compounds whose crystal structures are known, experimental enthalpies of sublimation correspond reasonably well to crystal lattice enthalpies predicted theoretically as the sum of electrostatic, dispersive and repulsive interactions. Analysis of crystal lattice enthalpy contributions indicates that dispersive interactions between molecules always predominate in the case of acridine derivatives, whilst the crystal lattices of their quaternary salts are stabilised by electrostatic interactions between ions. Only in the case of 9-bromomethylacridine derivative, which crystallises in the monohydrated form, electrostatic contribution to the crystal lattice energy is significantly higher than in the other investigated acridines.
- Zadykowicz, Beata,Storoniak, Piotr
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- Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents
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With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
- Song, Di,Zhang, Nan,Zhang, Panpan,Zhang, Na,Chen, Weijin,Zhang, Long,Guo, Ting,Gu, Xiaotong,Ma, Shutao
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- Compound, pharmaceutical composition, medicine and application of compound, pharmaceutical composition and medicine in preparation of antibacterial products
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The invention particularly relates to a compound, a pharmaceutical composition, a medicine and application of the compound, the pharmaceutical composition and the medicine in preparation of antibacterial products. The seeking of a novel antibacterial target and the development of a novel chemical entity have important significance for solving the increasingly severe bacterial drug resistance problem at present, and the design of a compound entity acting on the FtsZ target is expected to be developed to obtain an antibacterial drug which has no influence on a host. The invention provides a 9-aralkyl-10-methylacridine quaternary ammonium salt derivative and a preparation method thereof, and the compound has significant bactericidal and/or bacteriostatic activity on gram-positive bacteria, has a good effect of inhibiting bacterial division protein FtsZ, and can be used for preparing antibacterial products.
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Paragraph 0090-0092
(2021/07/17)
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- Preparation method of 9-bromomethyl acridine
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The invention relates to a preparation method of 9-bromomethyl acridine, and belongs to the technical field of organic synthesis. The preparation method of the 9-bromomethyl acridine comprises the following steps: (1) dissolving 9-methyl acridine, N-bromosuccinimide and benzoyl peroxide into an organic solvent, carrying out a bromination reaction, and performing separation after the bromination reaction is completed to obtain the 9-bromomethyl acridine. The method is simple and easy to operate, high in safety, good in reaction process controllability, capable of effectively avoiding side reactions and suitable for large-scale preparation of the 9-bromomethyl acridine, and the 9-bromomethyl acridine prepared through the method is high in yield and purity.
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Paragraph 0027-0060
(2020/08/09)
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- 3-[(E)-(acridin-9′-ylmethylidene)amino]-1-substituted thioureas and their biological activity
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This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV–vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8?×?104?M??1 and the percentage of hypochromism was found to be 22.11–49.75% (from UV–vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60?×?10??6?M.
- Be?ka, Michal,Vilková, Mária,Salem, Othman,Ka?párková, Jana,Brabec, Viktor,Ko?urková, Mária
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p. 234 - 241
(2017/03/23)
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- Imaging Beta-Amyloid Peptides Aggregation
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The present invention is in the field of pharmaceuticals and chemical industries. In particular, one aspect of the present invention relates to methods for labeling, imaging and detecting the beta-amyloid (Aβ) peptides, oligomers, and fibrils in vitro and in vivo via magnetic resonance and florescence imaging by using modified carbazole-based fluorophores. A further aspect of the present invention relates to a method of reducing and preventing aggregation of beta-amyloid peptides for Alzheimer's disease (AD) as well as of treating and/or preventing Alzheimer's disease by using the modified carbazole-based fluorophore. The modified carbazole-based fluorophore according to an embodiment of the present invention is prepared by conjugating a carbazole-based fluorophore with magnetic nanoparticles to form a conjugate which is permeable to blood brain barrier of a subject being introduced therewith.
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Paragraph 0115
(2016/09/26)
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- Prediction by 13C NMR of regioselectivity in 1,3-dipolar cycloadditions of acridin-9-yl dipolarophiles
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Strong correlation was found between 13C NMR chemical shifts of dipolarophilic CH=CH carbons and regioselectivity in 1,3-dipolar cycloadditions of new acridin-9-yl dipolarophiles with stable benzonitrile oxides (BNO). Accordingly, two starting
- Vilková, Mária,Ungvarská Ma?u?ká, Lucia,Imrich, Ján
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- Spontaneous cyclization of (acridin-9-ylmethyl)thioureas to spiro [dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones, a novel type of acridine spirocycles
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Novel acridine spirocompounds, spiro[dihydroacridine-9′(10′H), 5-imidazolidine]-2-thiones have been prepared by the spontaneous cyclization of 1-substituted 3-(acridin-9-ylmethyl)thioureas, which were obtained from 1-(acridin-9-yl)methanamine, N-(acridin-9-ylmethyl)propan-1-amine, and N-(acridin-9-ylmethyl)benzylamine and alkyl/aryl isothiocyanates, as continuation of our previous studies on new acridine spirocycles. Imidazolidine-2-thiones thus obtained were subsequently transformed with mesitylnitrile oxide to imidazolidine-2-one analogues, some of which partly reopened to the corresponding (acridin-9-ylmethyl)ureas. An unusual spirocyclization via a CH carbanion instead of the N-1 nitrogen has been found for 3-(acridin-9-ylmethyl)-1-(acridin-9-yl)thioureas possessing two acridine rings. Structural modifications in positions 1, 3, and 4 of the spiro ring together with 1H, 13C, and 15N NMR spectroscopy and X-ray crystallography have been employed to rationalize a general propensity of various 9-substituted acridines to undergo easy spirocyclization.
- Vilková, Mária,Prokaiová, Marianna,Imrich, Ján
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p. 944 - 961
(2014/01/23)
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- Fluorescent photoremovable precursor (acridin-9-ylmethyl)ester: Synthesis, photophysical, photochemical and biological applications
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A series of carboxylic acids including amino acids were protected as their corresponding fluorescent ester conjugates by coupling with an environment sensitive fluorophore 9-methylacridine. Photophysical properties of all the ester conjugates along with the protecting group have been investigated. Interestingly, the emission properties of the ester conjugates and 9-methylacridine were found to be highly sensitive to polarity, H-bonding and pH of the environment. Photolysis of all the ester conjugates was carried out using UV light above 360 nm and it was found that in every case the corresponding carboxylic acids were released in high chemical yield. Further, intercalation and the preferred binding mode of acridine-9-methanol and its ester conjugates with DNA were studied. In vitro biological studies revealed that acridine-9-methanol has good biocompatibility, cellular uptake property and cell imaging ability. The Royal Society of Chemistry and Owner Societies 2013.
- Jana, Avijit,Saha, Biswajit,Karthik,Barman, Sharabani,Ikbal, Mohammed,Ghosh, Sudip Kumar,Pradeep Singh
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p. 1041 - 1052
(2013/09/12)
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- Imaging Beta-Amyloid Peptides and Inhibition of Beta-Amyloid Peptide Aggregation
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The present invention relates to methods of detecting and monitoring aggregation of beta-amyloid peptides which are associated with neurodegenerative diseases as well as treating and/or preventing the neurodegenerative diseases by using carbazole-based fluorophores. In particular, the present invention provides methods for labeling and imaging the beta-amyloid (Aβ) peptides, oligomers, and fibrils in vitro and/or in vivo, as well as treating and/or preventing Alzheimer's disease by using the carbazole-based fluorophores of the present invention.
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- Novel carbohydrazide and hydrazone biomarkers based on 9-substituted acridine and anthracene fluorogens
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Three series of carbohydrazides or hydrazones bearing either acridine or anthracene pharmacophores were synthesized as potential noncovalent DNA-binding antitumor agents. Carbohydrazides with an acridine or anthracene moiety were prepared from appropriate acridine or anthracene carbaldehydes via cyclocondensation with selected hydrazides whilst hydrazones with a 10H-acridin-9-ylidene moiety were obtained by condensation of (acridin-9-yl)hydrazine with various aldehydes or ketones. The spectroscopic properties of the first two series revealed efficient fluorescence implying that the compounds could be amenable for use as biomarkers. The structures of the compounds were characterized by spectral methods (UV-vis, fluorescence, IR, and 1H, 13C, and 2D NMR) and quantum-chemical calculations (DFT, ZINDO, and AM1). The first carbohydrazide series was also tested against human leukemia cell line HL-60 wherein the phenyl-substituted derivative was found to possess the highest activity.
- Bedlcoviova, Zdenka,Imrich, Jn,Kristian, Pavol,Danihel, Ivan,Boehm, Stanislav,Sabolova, Danica,Kozurkova, Maria,Paulikova, Helena,Klika, Karel D.
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experimental part
p. 1047 - 1066
(2010/10/21)
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