- Synthesis of novel carbohydrate acridinone derivatives with potential biological activities using 1,3-dipolar cycloaddition
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Novel 10-{[3-(6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)- 4,5-dihydro-5-isoxazolyl]methyl}-9(10H)-acridinone derivatives (13-16) were synthesized by 1,3-dipolar cycloaddition using the carbohydrate derivative as dipole and different 10-allyl-9(10H)-acridinone derivatives (9-12) as dipolarophiles. The new cycloadducts as well as the dipolarophiles precursors were characterized spectroscopically. Copyright Taylor & Francis Group, LLC.
- Fascio, Mirta L.,D'Accorso, Norma Beatriz,Pellon, Rolando F.,Docampo, Maite L.
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- Improving the fluorescent probe acridonylalanine through a combination of theory and experiment
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Acridonylalanine (Acd) is a useful fluorophore for studying proteins by fluorescence spectroscopy, but it can potentially be improved by being made longer wavelength or brighter. Here, we report the synthesis of Acd core derivatives and their photophysical characterization. We also performed ab initio calculations of the absorption and emission spectra of Acd derivatives, which agree well with experimental measurements. The amino acid aminoacridonylalanine (Aad) was synthesized in forms appropriate for genetic incorporation and peptide synthesis. We show that Aad is a superior F?rster resonance energy transfer acceptor to Acd in a peptide cleavage assay and that Aad can be activated by an aminoacyl tRNA synthetase for genetic incorporation. Together, these results show that we can use computation to design enhanced Acd derivatives, which can be used in peptides and proteins.
- Sungwienwong, Itthipol,Ferrie, John J.,Jun, Joomyung V.,Liu, Chunxiao,Barrett, Taylor M.,Hostetler, Zachary M.,Ieda, Naoya,Hendricks, Amara,Muthusamy, Anand K.,Kohli, Rahul M.,Chenoweth, David M.,Petersson, George A.,Petersson, E. James
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supporting information
(2018/02/27)
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- Design, synthesis, in vitro cytotoxic activity evaluation, and apoptosis-induction study of new 9(10H-acridinone-1,2,3-triazoles
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A new series of 9(10H-acridinone-1,2,3-triazole derivatives were designed, synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. The acridone skeleton was prepared through the Ullman condensation of 2-bromobenzoic acid and anilines. Subsequently, it was functionalized with propargyl bromide. Then, a click reaction of the latter compound and in situ prepared 1-(azidomethyl)-4-methoxybenzene derivatives led to the formation of the desired triazole products. Finally, all products were investigated for their capability to cause cytotoxicity against MCF-7, T-47D, and MDA-MB-231 cell lines. Among them, 2-methoxy-10-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H-one 8c exhibited the most potency (hbox {IC}_{50},{=},11.0,{pm }, 4.8, upmu hbox {M})(IC50=11.0±4.8μM) against MCF-7 cells, being more potent than etoposide (hbox {IC}_{50},{=}, 12.4,{pm }, 4.7 upmu hbox {M})(IC50=12.4±4.7μM). Also, apoptosis induced by compound 8c was confirmed via acridine orange/ethidium bromide and Annexin V-FITC/propidium iodide (PI) double staining.
- Mohammadi-Khanaposhtani, Maryam,Safavi, Maliheh,Sabourian, Reyhaneh,Mahdavi, Mohammad,Pordeli, Mahboobeh,Saeedi, Mina,Ardestani, Sussan Kabudanian,Foroumadi, Alireza,Shafiee, Abbas,Akbarzadeh, Tahmineh
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p. 787 - 795
(2015/10/12)
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- Design, synthesis, biological evaluation, and docking study of acetylcholinesterase inhibitors: New acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids
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In this study, novel acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10-((1-((3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 10b showed the most potent anti-acetylcholinesterase activity (IC50 = 11.55 μm) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b. A novel series of acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities.
- Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad,Saeedi, Mina,Sabourian, Reyhaneh,Safavi, Maliheh,Khanavi, Mahnaz,Foroumadi, Alireza,Shafiee, Abbas,Akbarzadeh, Tahmineh
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p. 1425 - 1432
(2016/02/05)
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- Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and v
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Cathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in many pathological conditions. This report describes the synthesis and evaluation of a series of N-arylanthranilic acids, acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics revealed that compounds of the classes of acridones are reversible competitive inhibitors of the target enzyme with affinities in the low micromolar range. They represent promising lead candidates for the discovery of novel competitive cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4-quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were uncompetitive inhibitors.
- Marques, Emerson F.,Bueno, Mauro A.,Duarte, Patricia D.,Silva, Larissa R.S.P.,Martinelli, Ariani M.,Dos Santos, Caio Y.,Severino, Richele P.,Broemme, Dieter,Vieira, Paulo C.,Correa, Arlene G.
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- Synthesis and evaluation of N-Benzyl-acridinone derivatives induced apoptosis in human liver cancer cell-lines
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A series of N-benzyl-9(10H)-acridinones were synthesized and tested for their antitumor activities in vitro against HepG2 cells Assay-based antiproliferative activity study using HepG2 cell lines revealed that several compounds had significant effects on cytotoxicity, among which compound 5h was found to be the most active compound with IC50 at about 1.33 μM using the MTT assay. The antitumor effect of compound 5h is believed to be due to the induction of apoptosis, which was further confirmed by Hoechst 33258 fluorescence staining, agarose gel electrophoresis and Annexin VFITC/ PI staining assay using flow cytometry analysis. Above all, compound 5h would be a potential anticancer agent which deserves further research.
- Huang, Xian-Feng,Yulan-Zhua,Zhu, Hai-Liang
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p. 606 - 611
(2012/06/04)
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- An efficient synthesis of 9(10H)-acridinones under microwaves
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N-Phenylarithranilic acids have been subjected to cyclisation with different catalysts like silica gel, acidic alumina, strongly acidic montmorillonite (K10) clay, acetic acid, PTSA or Lewis acids like ZnCl 2, AlCl3 and PPA under microwave irradiation to give 9(10H)-acridinones of which PPA has been found to be the best catalyst for cyclisation.
- Nadaraj,Kalaivani,Selvi, S. Thamarai
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p. 1958 - 1960
(2007/10/03)
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- Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells.
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Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBChR-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study on the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBChR-8-5 cells or anti-MDR activity.
- Hedge, Ravi,Thimmaiah, Padma,Yerigeri, Mayur C.,Krishnegowda, Gowdahalli,Thimmaiah, Kuntebommanahalli N.,Houghton, Peter J.
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p. 161 - 178
(2007/10/03)
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- Acridinylresorcinol as a self-complementary building block of robust hydrogen-bonded 2D nets with coordinative saturation. Preservation of crystal structures upon guest alteration, guest removal, and host modification
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Acridinylresorcinol host 3 (9-(3,5-dihydroxy-1-phenyl)acridine) forms such adducts as 3·(benzene), 3·(chloroform), 3·0.5(toluene), and 3·(isobutyl benzoate). Modified acridinol host 4 (9-(3,5-dihydroxy-1-phenyl)-4-hydroxyacridine) having an additional OH group on the acridine ring affords such adducts as 4·(benzene), 4·(chloroform), 4·0.5(toluene)·0.5(water), 4·(methanol)·(water), and 4·(ethyl acetate). In the crystals, hosts 3 and 4 form hydrogen-bonded (O-H...O-H) poly(resorcinol) chains which are linked together via interchain O-H...N hydrogen bonds to give a coordinatively saturated (O-H...O-H...N) 2D net composed of doubly hydrogen-bonded and antiparallel-stacked, self-complementary cyclic dimer 32 or 42 as a rigidified building block, the otherwise flexible O-H...O-H hydrogen bonds being thereby taken in a cyclophane-like structure. This network turns out to be remarkably well preserved among the above adducts. Guest molecules, which are disordered in many cases, are incorporated in the cavities left. The binding of small polar guests to host 4 is primarily due to hydrogen bonding to the OH group on the acridine ring. The latter therefore acts only as a polarity modifier of preserved cavities. Adduct 3·(benzene), that is, 32·2(benzene) readily loses one of two guest molecules bound in each cavity to give a microporous half-filled adduct 32·(benzene) which adsorbs 1 mol of benzene to regenerate the starting full adduct without involving a phase change, as confirmed by X-ray powder diffractions and reversible Langmuir-type adsorption/desorption isotherms. The self-complementarity strategy for designing rigid crystal structures is discussed with a particular reference to the possibility of systematic perturbation/variation approaches in crystal engineering.
- Tanaka, Toshihiro,Tasaki, Takashi,Aoyama, Yasuhiro
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p. 12453 - 12462
(2007/10/03)
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- Reaction of 4-hydroxyacridin-9(10H)-one and 4-hydroxyacridine-9(10H)-thione with α,ω-alkyl dibromides
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Starting from 4-hydroxyacridin-9(10H)-one (1) and 4-hydroxyacridine-9(10H)-thione (2), a series of bis-derivatives was prepared, among them the bridged bis-acridin-(10H)-ones 9-14 and the bis-mercapto-(9H)-acridines 15-18. The reactivity of the 2-and 4-hydroxy series was compared; it was found that it is harder to demethylate 4-methoxy derivatives than their 2-methoxy analogues.
- Galy, Jean-Pierre,Galy, Anne-Marie,Vichet, Alain,Elguero, Jose
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p. 1199 - 1205
(2007/10/03)
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- An In-depth Study of the Azidobenzophenone-Anthranil-Acridone Transformation
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The title transformation, particularly the conversion of anthranils into acridones, is shown to be critically sensitive to temperature, solvent, substituent, and metal catalysts.Thus the conversion of 3-(p-tolyl)anthranil into an acridone gives a ratio of 2-and 3-methyl derivatives varying from 0.6:1 to 4.7:1 with changing temperature and solvent.In other similar thermolyses, solvents (e.g. 1,2,4-trichlorobenzene) were incorporated into the product and traces of metals and their derivatives had a dramatic effect on the rate and course of the reaction.The most effective catalysts were iron powder and aluminium acetylacetonate. 3-(2,6-Disubstituted phenyl)anthranils gave acridones in which the substituents were either lost or rearranged onto N or C, the last cases involving sequential -sigmatropic shifts. 3-Thienylanthranils gave related thienoquinolones on thermolysis; again the reaction were very sensitive to catalysis.Blocked thienylanthranils also gave rearrangement products, but the non-aromatic intermediates could be isolated.
- Hawkins, David G.,Meth-Cohn, Otto
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p. 2077 - 2087
(2007/10/02)
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- Organic photochemical reactions-V. Photorearrangement of anthranils into azepines
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The photolysis of anthranils (III) led to ring enlargement with the formation of 3-acyl-2-methoxy-3H-azepines (IV). The reaction in ether containing water or amines yielded the corresponding 2-oxo- or 2-amino-3H-azepines (V or VII). On the other hand, photolysis of some 7-substituted 3-phenylanthranils (IX and XIII) gave the corresponding 9-acridanone derivatives (X and XIV). A hypothetical scheme (anthranil → nitrene → azirene → azepine) similar to that proposed by Huisgen and Appl for the analogous ring enlargement of phenylazide is applicable to the anthranil rearrangement. By UV and IR spectroscopic methods, the last step was proved to involve a dark reaction of an intermediate (probably azirene species) with protic solvents.
- Ogata,Matsumoto,Kano
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p. 5205 - 5215
(2007/10/07)
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