- Assessment of dna topoisomerase i unwinding activity, radical scavenging capacity, and inhibition of breast cancer cell viability of n-alkylacridones and n,n′-dialkyl-9,9′-biacridylidenes
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The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of N-alkyl-acridones 1–6 and N,N′-dialkyl-9,9′-biacridylidenes 7–12 with variable alkyl chains were examined for their topoisomerase I activity at neutral and acidic conditions as well as for their binding capacity to calf thymus and possible radical trapping antioxidant activity. It was found that at a neutral pH, topoisomerase I activity of both classes of compounds was similar, while under acidic conditions, enhanced intercalation was observed. Nalkyl- acridone derivatives 1–6 exhibited stronger, dose-dependent, cytotoxic activity against MCF- 7 human breast epithelial cancer cells than N,N′-dialkyl-9,9′-biacridylidenes 7–12, revealing that conjugation of the heteroaromatic system plays a significant role on the effective distribution of the compound in the intracellular environment. Cellular investigation of long alkyl derivatives against cell migration exhibited 40–50% wound healing effects and cytoplasm diffusion, while compounds with shorter alkyl chains were accumulated both in the nucleus and cytoplasm. All N,N′-dialkyl- 9,9′-biacridylidenes showed unexpected high scavenging activity towards DPPH or ABTS radicals which may be explained by higher stabilization of radical cations by the extended conjugation of heteroaromatic ring system.
- Krokidis, Marios G.,Molphy, Zara,Efthimiadou, Eleni K.,Kokoli, Marianna,Argyri, Smaragda-Maria,Dousi, Irini,Masi, Annalisa,Papadopoulos, Kyriakos,Kellett, Andrew,Chatgilialoglu, Chryssostomos
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- Synthesis, cytotoxicity evaluation, and molecular modeling studies of 2,N10-substituted acridones as DNA-intercalating agents
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Acridine-based compounds possess anticancer activities by intercalating to DNA. Although they have chemotherapeutic potential, acridine-based compounds are not used to treat cancer. In this study, 2,N10-acridone derivatives are designed and synthesized based on acridone, a ketone derivative of acridine. Herein, acridone is functionalized with alkyl side chains containing terminal nitrogen-based moieties at the N10-position and substituted at the C2-position. The products are evaluated for in vitro cytotoxicity against four cancer cell lines: Molt-3, HepG2, A549, and HuCCA-1. The derivative bearing two butyl piperidine side chains at the C2- and N10-positions is the most active, with IC50 values ranging from 2.96 to 9.46 μM. Molecular modeling studies supported the binding of the derivatives to DNA by intercalation, thereby confirming the observed cytotoxic effects.
- Chimnoi, Nitirat,Eurtivong, Chatchakorn,Jumpathong, Watthanachai,Khunnawutmanotham, Nisachon,Techasakul, Supanna
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p. 410 - 425
(2020/03/23)
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- Synthesis of Acridones by Palladium-Catalyzed Buchwald-Hartwig Amination
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The Buchwald-Hartwig amination allows an efficient and convenient synthesis of biologically and pharmaceutically important acridones by formation of a six-membered ring. With the described method, a number of derivatives have been synthesized in up to 95% yield by using a variety of anilines as well as benzylic and aliphatic amines.
- Janke, Julia,Villinger, Alexander,Ehlers, Peter,Langer, Peter
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p. 817 - 820
(2019/04/25)
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- Synthesis method of acridone derivative
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The application relates to a synthesis method of an acridone derivative. The synthesis method comprises the following steps: mixing a compound shown in a formula (I), a photocatalyst and a solvent, reacting under the conditions of oxygen and lighting and obtaining the acridone derivative. The synthesis method of the acridone derivative has the beneficial effects that the photocatalyst can catalyzethe compound shown in the formula (I) to carry out intramolecular hydrocarbon ammoniation reaction under the conditions of oxygen and lighting so as to synthesize the acridone derivative, and the pretreatment for the compound shown in the formula (I) is not needed; the operation is simple and convenient, and the condition is mild, the yield is high; the synthesis method conforms to the economic and environment-friendly characteristics of atoms and has high practical value for industrial preparation of the acridone derivative.
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Paragraph 0047-0049; 0116-0118; 0123-0125; 0067-0069
(2019/01/05)
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- Transition-Metal-Free Synthesis of Acridones via Base-Mediated Intramolecular Oxidative C?H Amination
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Intramolecular oxidative C?H amination of 2-aminobenzophenones was achieved in the presence of potassium tert-butoxide and dimethyl sulfoxide. A series of functionalized acridones were prepared in moderate to excellent yields in a mild, efficient, and transition-metal-free manner. (Figure presented.).
- Wei, Wen-Tao,Sheng, Jian-Fei,Miao, Hui,Luo, Xiang,Song, Xian-Heng,Yan, Ming,Zou, Yong
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p. 2101 - 2106
(2018/06/14)
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- Anisotropic Dissociation of π-π Stacking and Flipping-Motion-Induced Crystal Jumping in Alkylacridones and Their Dicyanomethylene Derivatives
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Ethylacridone (1 b) and dicyanomethylenated acridones 2 a,b,d showed crystal-jumping activity upon heating. This is the first example of thermosalient behavior in a simple aromatic ketone and its derivatives. A systematic investigation of the jumping behavior of derivatives with different alkyl chains by variable-temperature X-ray crystal-structure analyses revealed the mechanism of this phenomenon. Anisotropic dissociation of π stacking in a dimer was important for inducing crystal jumping in 1 b, whereas the collective fluctuation/flipping motion of a dicyanomethylene unit induced crystal jumping in 2.
- Takeda, Takashi,Akutagawa, Tomoyuki
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p. 7763 - 7770
(2016/06/08)
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- 3-Substituted biquinolinium inhibitors of AraC family transcriptional activator VirF from S. flexneri obtained through in situ chemical ionization of 3,4-disubstituted dihydroquinolines
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During a structure-activity relationship optimization campaign to develop an inhibitor of AraC family transcriptional activators, we discovered an unexpected transformation of a previously reported inhibitor that occurs under the assay conditions. Once pl
- Jain, Prashi,Li, Jiaqin,Porubsky, Patrick,Neuenswander, Benjamin,Egan, Susan M.,Aub, Jeffrey,Rogers, Steven
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p. 39809 - 39816
(2015/02/05)
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- Microwave-promoted N-alkylation of acridones without solvent
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N-Alkylacridones (3) were effectively synthesized in few minutes by reaction of acridone and alkyl halides with NaOH/K2CO3 absorbed on Al2O3 in the presence of TBAB under microwave irradiation without solvent.
- Wang, Cunde,Hang, Tianlong,Zhang, Hui
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p. 451 - 456
(2007/10/03)
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- A Convenient Preparation of Some N-Alkylcarbazoles and N-Alkylacridones
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N-Alkylation of aromatic compounds involving nitrogen heterocycles such as carbazole and acridone with alkyl halide in the presence of caustic solution and benzyl triethyl ammonium chloride (BTEAC) as a phase-transfer catalyst readily proceeded under mild conditions.These results show that this procedure is effective for the preparation of the title compounds in high yields.
- Nishi, Hisao,Kohno, Hisao,Kano, Toshihiro
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p. 1897 - 1898
(2007/10/02)
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