- Synthesis, cytotoxicity and structure-activity relationships between ester and amide functionalities in novel acridine-based platinum(II) complexes
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In order to improve the pharmacological profile of the anticancer drug cisplatin, several new acridine-based tethered (ethane-1,2-diamine)platinum(II) complexes connected by a polymethylene chain were synthetized. Activity-structure relationship between amide or ester functionalities was explored by changing acridine-9-carboxamide into acridine-9-carboxylate chromophore. The in vitro cytotoxicity of these new complexes was assessed in human colic HCT 116, SW480 and HT-29 cancer cell lines. Series of complexes bearing the acridine-9-carboxylate chromophore displayed higher cytotoxic effect than acridine-9-carboxamide complexes, with gradual effect according to the size of the polymethylene linker.
- Bouyer, Florence,Moretto, Johnny,Pertuit, David,Szollosi, Anna,Lacaille-Dubois, Marie-Aleth,Blache, Yves,Chauffert, Bruno,Desbois, Nicolas
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- A nitroxyl synthase catalytic antibody
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An antibody raised against acridinium hapten 1 is shown to catalyze the retro Diels-Alder reaction of the anthracene-HNO cycloadduct 2 to release anthracene 4 and nitroxyl (HNO). Nitroxyl is oxidized to nitric oxide (NO) in the presence of superoxide dism
- Bahr, Nicolaus,Güller, Rolf,Reymond, Jean-Louis,Lerner, Richard A.
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- Study of a potential inhibitor of acetylcholinesterase using UV spectrophotometry, NMR spectroscopy and molecular modeling
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1-[6-(Acridine-9-carbonyloxy)hexyl]pyridinium chloride (1) was synthesized and studied as a potential inhibitor of acetylcholinesterase (AChE), which is frequently involved in Alzheimer's disease. UV spectrophotometry showed that 1 is a reversible and competitive inhibitor of AChE (Ki ≈ 2 × 10-7 M). NMR (TrNOESY) showed that 1, bonded to AChE, maintains an extended form that allows hydrophobic interactions to occur between the aliphatic chain and the deep and narrow gorge of AchE and favors interactions between the acridine group and the catalytic and anionic subsites situated at the bottom of the gorge, and also between the pyridinium ring and the peripheral site. A more detailed picture of the structure of the complex was obtained by combining NMR structural data and molecular modeling (docking, dynamics simulation and energy calculations). Copyright
- Correia, Isabelle,Ronzani, Nello,Platzer, Nicole,Doan, Bich-Thuy,Beloeil, Jean-Claude
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- Synthesis and characterization of polyamine-based biomimetic catalysts as artificial ribonuclease
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Several polyamine derivatives (I-V) conjugated with or without an intercalative moiety were prepared as ribonuclease mimics. Although no DNA-cleaving activity was observed for all compounds tested, mimics I, III, and V bearing an intercalative moiety alon
- Shinozuka,Nakashima,Shimizu,Sawai
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Read Online
- Synthesis and antimicrobial activity of acridine carboxylic acid derivatives containing a piperazine moiety
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A convenient method for the synthesis of new acridine derivatives containing a piperazine moiety was developed. Antimicrobial activity against some pathogenic microorganisms was established for a series of the synthesized compounds.
- Kudryavtseva,Lamanov, A. Yu.,Klimova,Nazarov
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Read Online
- Metal complexes of modified cyclen as catalysts for hydrolytic restriction of plasmid DNA
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Simple and novel nuclease models have been synthesized. These involve metal-binding ligand 1,4,7,10-tetraazlcyclododecane (cyclen) tethered to an acridine ring (a DNA-binding group) by amide linkers of various lengths. Binding of these probes to DNA was s
- Krauser, Joel A.,Joshi, Aarti L.,Kady, Ismail O.
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- 9-(2,6-Difluorophenoxycarbonyl)-10-methylacridinium trifluoromethane- sulfonate and its precursor 2,6-difluorophenyl acridine-9-carboxylate: C-H...O, C-F...π, S-O...π and π-π stacking interactions
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The title compounds, C21H14F2NO 2+·CF3SO3-, (I), and C20H11F2NO2, (II), form monoclinic and triclinic crystals, respectivel
- Sikorski, Artur,Krzyminski, Karol,Niziolek, Agnieszka,Blazejowski, Jerzy
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Read Online
- A Novel Multifunctionally Labelled DNA Probe Bearing an Intercalator and a Fluorophore
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A 15-mer DNA labelled with a novel multifunctional fluorescent agent bearing acridine and fluorescein moieties is synthesized and the intensity of fluorescein-based fluorescence detected by the excitation of acridine is shown to be strongly affected by the DNA's secondary structure.
- Shinozuka, Kazuo,Seto, Yoshiaki,Sawai, Hiroaki
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- DINUCLEATING LIGAND OR DINUCLEAR METAL COMPLEX
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To provide a dinuclear metal complex that can be synthesized simply and easily and has a proper anticancer action.SOLUTION: The present disclosure provides a dinucleating ligand represented by the following formula (I) and a dinuclear metal complex thereof (where each X may be the same or different to represent H, Cl, OMe, or, Me, Y is H, a phenyl group, a substituted carbamoyl group or the like).SELECTED DRAWING: None
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Paragraph 0112-0113
(2021/03/19)
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- AMINE OR (THIO)AMIDE CONTAINING LXR MODULATORS
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The present invention relates to derivatives of formula (I) which bind to the liver X receptor (LXRα and/or LXRβ) and act preferably as inverse agonists of LXR.
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Page/Page column 81
(2019/02/06)
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- Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency
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Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very differen
- Felip-León, Carles,Martínez-Arroyo, Olga,Díaz-Oltra, Santiago,Miravet, Juan F.,Apostolova, Nadezda,Galindo, Francisco
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supporting information
p. 869 - 874
(2018/02/21)
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- Novel methylselenoesters as antiproliferative agents
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Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.
- Díaz-Argelich, Nuria,Encío, Ignacio,Plano, Daniel,Fernandes, Aristi P.,Palop, Juan Antonio,Sanmartín, Carmen
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- Preparation method of compound reacting with alkaline phosphatase to create chemiluminiscence
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The invention relates to a preparation method of a compound reacting with alkaline phosphatase to create chemiluminiscence. The preparation method comprises the following synthesizing steps in sequence: (1) synthesizing acridine-9-sulfuryl chloride; (2) s
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Paragraph 0019; 0022
(2017/08/29)
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- An acridine hydrazone derivatives and its preparation and use
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The invention provides acridine acylhydrazone derivatives which are characterized in that the structural formula is disclosed in the specification. The invention also provides a preparation method and application of the acridine acylhydrazone derivatives. The preparation method is simple and has high operability. The acridine acylhydrazone derivatives simultaneously contain the two types of active structures acridine and acylhydrazone, and thus, have higher potential bioactivity. The in-vitro antitumor test indicates that the compounds have high inhibiting action on all tested tumor cells and can be further developed as an antineoplastic drug or lead compound.
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Paragraph 0027
(2016/10/10)
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- Structure, formation, thermodynamics and interactions in 9-carboxy-10-methylacridinium-based molecular systems
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9-Carboxy-10-methylacridinium chloride and trifluoromethanesulfonate, the parent compounds for a wide range of chemiluminogenic salts of practical importance, were synthesized and thoroughly investigated to address problems concerning structural and thermodynamical issues of these cognitively interesting molecular systems. Under various conditions of crystallization, the title salts disclosed three types of crystals: one built from the monomeric form of cations and two containing homoconjugated cations. The title compounds made the first described derivatives of acridine, expressing homoconjugated cationic forms, both in crystalline solid and gaseous phases. The monocrystals were characterized, employing X-ray crystallography and spectroscopic methods such as MALDI-TOF MS, ESI-QTOF MS, NMR and UV-Vis. X-ray crystallography studies revealed the occurrence of the three different molecular architectures, in which not only the counter ions and stoichiometry are different, but also the space group and number of molecules in the unit cell. The energetics and intermolecular interactions occurring within the crystals were explored, applying crystal lattice energy calculations and Hirshfeld surface analysis. In order to elucidate the thermodynamics and origin of the experimentally revealed forms, computations based on the density functional theory were performed, assuming vapour and liquid phases.
- Trzybiński, Damian,Zadykowicz, Beata,Wera, Micha?,Serdiuk, Illia E.,Sieradzan, Andrzej,Sikorski, Artur,Storoniak, Piotr,Krzymiński, Karol
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supporting information
p. 7359 - 7372
(2016/09/12)
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- Effective chemiluminogenic systems based on acridinium esters bearing substituents of various electronic and steric properties
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A series of 10-methyl-9-(phenoxycarbonyl)acridinium trifluoromethanesulfonates (XAEs), bearing substituents of various characteristics in the lateral benzene ring (2-halogen, 2,6-dihalogen, 2-trifluoromethyl, 2-nitro, 2-methoxy, 3-halogen and 4-halogen) w
- Zadykowicz, Beata,Czechowska, Justyna,Ozóg, Agnieszka,Renkevich, Anton,Krzymiński, Karol
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supporting information
p. 652 - 668
(2016/01/12)
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- Enzyme-artificial enzyme interactions as a means for discriminating among structurally similar isozymes
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We describe the design and function of an artificial enzyme-linked receptor (ELR) that can bind different members of the glutathione-S-transferase (GST) enzyme family. The artificial enzyme-enzyme interactions distinctly affect the catalytic activity of the natural enzymes, the biomimetic, or both, enabling the system to discriminate among structurally similar GST isozymes.
- Selvakumar, Karuthapandi,Motiei, Leila,Margulies, David
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supporting information
p. 4892 - 4895
(2015/05/05)
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- Structural variations on antitumour agents derived from bisacylimidoselenocarbamate. A proposal for structure-activity relationships based on the analysis of conformational behaviour
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A molecular modelling study has been carried out on a previously reported series of symmetrically substituted bisacylimidoselenocarbamate (BSeC) derivatives that show remarkable antitumour activity in vitro against a panel of human tumour cell lines. These derivatives can be considered as a central scaffold constructed around a methyl carbamimidoselenoate nucleus in which two heteroarylacyl fragments are located on the scaffold nitrogen atoms, thus forming the different BSeCs. The results reveal that the nature of the selected heteroaryl ring has a marked influence on the antiproliferative activity of the compounds and this can be related, as a first approximation, to the ability to release methylselenol (MeSeH), a compound that, according to our initial hypothesis, is ultimately responsible for the antitumour activity of the compounds under investigation. The release of MeSeH from the active BSeCs has been confirmed by means of Head Space Gas Chromatography Mass Spectrometry techniques. The data that support this connection include the topography of the molecules, the conformational behaviour of the compounds, which influences the accessibility of the hydrolysis point, the interaction map obtained for an O2H type probe, and the location and energy of the HOMO/LUMO orbitals.
- Font, María,Lizarraga, Elena,Ibá?ez, Elena,Plano, Daniel,Sanmartiń, Carmen,Palop, Juan A.
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supporting information
p. 489 - 498
(2013/10/01)
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- 1H and 13C NMR spectra, structure and physicochemical features of phenyl acridine-9-carboxylates and 10-methyl-9-(phenoxycarbonyl) acridinium trifluoromethanesulphonates - alkyl substituted in the phenyl fragment
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The 1H and 13C NMR spectra of twelve phenyl acridine-9-carboxylates - alkyl-substituted in the phenyl fragment - and their 10-methyl-9-(phenoxycarbonyl)acridinium salts dissolved in CD3CN, CD3OD, CDCl3/sub
- Krzymiński,Malecha,Zadykowicz,Wróblewska,B?aejowski
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experimental part
p. 401 - 409
(2011/03/21)
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- Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates
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The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymphocytic leukemia (K-562), hepatocarcinoma (Hep-G2), prostate cancer (PC-3) and one non-malignant mammary gland-derived cell line (MCF-10A). The GI50 values for eighteen of the compounds were below 10 μM in at least one cell line. Two cancer cells (MCF-7 and HT-29) proved to be the most sensitive to five compounds (1b, 2b, 3b, 4b and 5b), with growth inhibition in the nanomolar range, and compounds 1b, 3b, 7b, 8b and 9b gave values of less than 1 μM. In addition, all of the aforementioned compounds exhibited lower GI50 values than some of the standard chemotherapeutic drugs used as references. The results also reveal that the nature of the aliphatic chain (methyl is better than benzyl) at the selenium position and the nature of the heteroatom (Se better than S) have a marked influence on the antiproliferative activity of the compounds. These findings reinforce our earlier hypothesis concerning the determinant role of the selenomethyl group as a scaffold for the biological activity of this type of compound. Considering both the cytotoxic parameters and the selectivity index (which was compared in MCF-7 and MCF-10A cells), compounds 2b and 8b (with a selenomethyl moiety) displayed the best profiles, with GI50 values ranging from 0.34 nM to 6.07 μM in the five cell lines tested. Therefore, compounds 2b and 8b were evaluated by flow cytometric analysis for their effects on cell cycle distribution and apoptosis in MCF-7 cells. 2b was the most active, with an apoptogenic effect similar to camptothecin, which was used as a positive control. Both of them provoked cell cycle arrest leading to the accumulation of cells in either G2/M and S phase. These two compounds can therefore be considered as the most promising candidates for the development of novel generations of antitumor agents.
- Ibá?ez, Elena,Plano, Daniel,Font, María,Calvo, Alfonso,Prior, Celia,Palop, Juan Antonio,Sanmartín, Carmen
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experimental part
p. 265 - 274
(2011/02/27)
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- Spectral features of substituted 9-(phenoxycarbonyl)-acridines and their protonated and methylated cation derivatives
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The long-wavelength absorption of eight 9-(phenoxycarbonyl)-acridines and the 10-H-9-(phenoxycarbonyl)-acridinium and 10-methyl-9-(phenoxycarbonyl)-acridinium cations derived from them, substituted with an alkyl or trifluoroalkyl group at the benzene ring
- Krzyminski, Karol,Roshal, Alexander D.,Niziolek, Agnieszka
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p. 394 - 402
(2008/09/21)
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- Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors
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In the context of the design and synthesis of minor groove binding and intercalating DNA ligands some new oligopyrrole carboxamides were synthesized. These hybrid molecules (combilexins) possess a variable and conformatively flexible spacer at the N-terminal end. As intercalating tricyclic systems acridone, acridine, anthraquinones and in a special case iminostilbene terminate the N-terminal end of the pyrrole chain. The cytotoxicity was examined by the NCI antitumor screening, furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA binding properties and topoisomerase inhibition effect of this new series of molecules.
- David-Cordonnier, Marie-Helene,Hildebrand, Marie-Paule,Baldeyrou, Brigitte,Lansiaux, Amelie,Keuser, Christoph,Benzschawel, Kerstin,Lemster, Thomas,Pindur, Ulf
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p. 752 - 771
(2008/02/13)
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- Monitoring oligonucleotide binding processes using chemiluminescence quenching
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Oligonucleotide building processes are monitored by means of an oligonucleotide probe which in one embodiment is labelled at one end with a chemiluminescent label and at the other end with a quencher molecule. The conformation of the oligonucleotide probe
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- Substituent effects on aromatic stacking interactions
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Synthetic supramolecular zipper complexes have been used to quantify substituent effects on the free energies of aromatic stacking interactions. The conformational properties of the complexes have been characterised using NMR spectroscopy in CDCl3, and by comparison with the solid state structures of model compounds. The structural similarity of the complexes makes it possible to apply the double mutant cycle method to evaluate the magnitudes of 24 different aromatic stacking interactions. The major trends in the interaction energy can be rationalised using a simple model based on electrostatic interactions between the π-faces of the two aromatic rings. However, electrostatic interactions between the substituents of one ring and the π-face of the other make an additional contribution, due to the slight offset in the stacking geometry. This property makes aromatic stacking interactions particularly sensitive to changes in orientation as well as the nature and location of substituents. This journal is The Royal Society of Chemistry.
- Cockroft, Scott L.,Perkins, Julie,Zonta, Cristiano,Adams, Harry,Spey, Sharon E.,Low, Caroline M. R.,Vinter, Jeremy G.,Lawson, Kevin R.,Urch, Christopher J.,Hunter, Christopher A.
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p. 1062 - 1080
(2007/12/27)
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- 9-(2,6-Dichlorophenoxycarbonyl)10-methylacridinium trifluoro- methanesulfonate and its precursor 2,6-dichlorophenyl acridine-9-carboxylate
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The title compounds, C21H14Cl2NO 2+·CF3O3S- (I), and C20H11Cl2NO2, (II), form triclinic crystals. Adjacent cations of (I) a
- Sikorski, Artur,Krzyminski, Karol,Konitz, Antoni,Blazejowski, Jerzy
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p. o227-o230
(2007/10/03)
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- 2-ethylphenyl acridine-9-carboxylate and 2,5-dimethylphenyl acridine-9-carboxylate
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The title compounds, 2-ethylphenyl acridine-9-carboxylate, C 22H17NO2, (I), and 2,5-dimethylphenyl acridine-9-carboxylate, C22H17NO2, (II), form triclinic and monoclinic crystals, respectiv
- Sikorski, Artur,Krzyminski, Karol,Konitz, Antoni,Blazejowski, Jerzy
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- Preparation of Fluorescent Nonpeptidic Neuropeptide Y Receptor Ligands: Analogues of the Quinazoline-type Anti-obesity Y5 Antagonist CGP 71683A
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As part of a programme to develop fluorescence-based methods for the study of the interactions between G-protein coupled receptors (GPCRs) and their ligands the preparation of low molecular weight fluorescence-labelled neuropeptide Y (NPY) Y5 a
- Li, Liantao,Mayer, Matthias,Schneider, Erich,Schreiber, Elvira,Bernhardt, Guenther,Peng, Shiqi,Buschauer, Armin
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p. 585 - 590
(2007/10/03)
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- Reagents for labeling SH groups, process for the preparation of them and method for labeling with them
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Disclosed are SH-labeling reagents containing acridine compounds represented by the following formula (I): whereinA represents the following group:—(CH2)m1—or—(CH2)m2—Q—(CH2)n—in which Q re
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- Design, synthesis, and evaluation of N-aroyloxy-2-thiopyridones as DNA photocleaving reagents
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N-Benzoyloxy-2-thiopyridone (12) was shown to induce single-strand nicks in duplex DNA upon irradiation with visible light (λ~350nm). This finding led to the design of a series of compounds, in which an acridinyl nucleus was covalently linked to the N-benzoyloxy-2-thiopyridone unit. These conjugates (15, 16, 17 and 18) were synthesized and evaluated as novel DNA photocleaving reagents. Optimal photocleaving activity was observed for conjugate 16, in which a flexible polymethylene spacer of 4 carbons was used to connect the aminoacridine entity to the thiopyridone. This compound was shown to cleave DNA at low μM concentrations and was approximately two-orders of magnitude more efficient than the parent N-benzoyloxy-2-thiopyridone (12). Furthermore, the DNA cleavage ladders induced by 16 and 12 were found to be identical and of no significant sequence selectivity. These data suggest that the N-aroyloxy-2-thiopyridones can be used for the design of new DNA photocleaving reagents with potential use as 'photofootprinting agents' or as 'site-directed photonucleases'. Copyright (C) 1999 Elsevier Science Ltd.
- Blom, Petra,Xiang, Alan X.,Kao, David,Theodorakis, Emmanuel A.
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p. 727 - 736
(2007/10/03)
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- Characterization of Acridancarboxylic Acid Derivatives as Chemiluminescent Peroxidase Substrates
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A new class of peroxidase substrates has been developed which produces chemiluminescence upon enzymatic oxidation. A wide variety of N-alkylacridancarboxylic acid derivatives including esters, thioesters, and sulfonamides are efficiently oxidized by a peroxidase and a peroxide to enzymatically produce the corresponding chemiluminescent acridinium compound. In conjunction with a peroxidase enhancer, continuous light emission with high light intensities and an extended duration are produced. Alternately, an appropriately designed acridan substrate produces a stable acridinium ester intermediate which can be accumulated and the chemiluminescence elicited as a burst of light by raising the pH. The effects of leaving groups and substitution on the acridan ring on the mechanism of light production are discussed. Peroxidase-catalyzed oxidation in the presence of a peroxide permits the detection of enzyme with subattomolar sensitivity and a broad linear dynamic range.
- Akhavan-Tafti, Hashem,Desilva, Renuka,Arghavani, Zahra,Eickholt, Robert A.,Handley, Richard S.,Schoenfelner, Barry A.,Sugioka, Katsuaki,Sugioka, Yumiko,Paul Schaap
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p. 930 - 937
(2007/10/03)
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- Chemiluminescent reactions using dihydroxyaromatic compounds and heterocyclic enol phosphates
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Novel methods and compositions which generate chemiluminescence are provided. The compositions comprise a heterocyclic enol phosphate compound and a dihydroxyaromatic compound in which the two hydroxy groups are separated by an even number of ring carbon
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- A Free Radical Route to the Benzazepines and Dibenzazepines
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Free radical ring expansion of six membered azocycles provides a new entry to the preparation of benzazepines and dibenzazepines.
- Zheng, Zhizhen Barbara,Dowd, Paul
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p. 7709 - 7712
(2007/10/02)
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- Polysubstituted aryl acridinium esters
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The present invention relates to novel acridinium esters which are useful as luminescent labels in specific binding assays such as immunoassays or nucleic acid hybridization assays. More particularly, polysubstituted aryl acridinium esters are highly stab
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