- N-o-substituted phenyl benzamide-4-methylamino acridine compound as well as preparation method and application thereof
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The invention discloses an N-o-substituted phenyl benzamide-4-methylamino acridine compound as well as a preparation method and application thereof. The compound is characterized in that the compoundis a compound with a structural formula shown as a formula I or pharmaceutically acceptable salt, ester or solvate thereof, wherein R1 is H, OCH3, OCH2CH3, F, Cl, Br, CF3, NO2 or straight-chain alkylwith a carbon atom number of 1-5; R2 is H, OCH3, OCH2CH3, F, Cl, Br, CF3, NO2 or straight-chain alkyl with a carbon atom number of 1 to 5; R3 is NH2, NHCH3, NHCH2CH3, OH, COOH, and SH, and R4 is H, OCH3 or linear alkyl with 1-5 carbon atoms and the like. The compound has the advantages that the compound can effectively inhibit DNA topoisomerase I, and proliferation of I-type HDAC and/or eukaryotictumor cells, and prevents and/or treats tumors.
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Paragraph 0024; 0025; 0036; 0037
(2020/05/05)
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- Synthesis and Antibacterial Activity of New N9-Substituted Acridine-9-amines
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A method for the synthesis of N9-substituted acridine-9-amines by reacting 9-chloroacridines with 2-(2-methyl-5- nitro-1H-imidazol-1-yl)ethanamine was developed. The synthesized compounds showed high antibacterial ability against B. subtilis bacteria compared with rivanol and metronidazole.
- Kudryavtseva,Bogatyrev,Sysoev,Klimova
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p. 157 - 159
(2019/04/13)
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- Design, synthesis and biological research of novel N-phenylbenzamide-4-methylamine acridine derivatives as potential topoisomerase I/II and apoptosis-inducing agents
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A series of novel N-phenylbenzamide-4-methylamine acridine derivatives were designed and synthesized based initially on the structure of amsacrine (m-AMSA). Molecular docking suggested that the representative compound 9a had affinity for binding DNA topoisomerase (Topo) II, which was comparable with that of m-AMSA, and furthermore that 9a could have preferential interactions with Topo I. After synthesis of 9a and analogues 9b-9f, these were all tested in vitro and the synthesized compounds displayed potent antiproliferative activity against three different cancer cell lines (K562, CCRF-CEM and U937). Among them, compounds 9b, 9c and 9d exhibiting the highest activity with IC50 value ranging from 0.82 to 0.91 μM against CCRF-CEM cells. In addition, 9b and 9d also showed high antiproliferative activity against U937 cells, with IC50 values of 0.33 and 0.23 μM, respectively. The pharmacological mechanistic studies of these compounds were evaluated by Topo I/II inhibition, western blot assay and cell apoptosis detection. In summary, 9b effectively inhibited the activity of Topo I/II and induced DNA damage in CCRF-CEM cells and, moreover, significantly induced cell apoptosis in a concentration-dependent manner. These observations provide new information and guidance for the structural optimization of more novel acridine derivatives.
- Zhang, Bin,Dou, Zhende,Xiong, Zheng,Wang, Ning,He, Shan,Yan, Xiaojun,Jin, Haixiao
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supporting information
(2019/10/28)
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- 4-methylaminoacridine-N-phenylbenzamide compound and preparation method and application thereof
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The invention discloses a 4-aminomethylacridine-N-phenylbenzamide compound and a preparation method and application thereof. The compound is characterized in that the compound is a compound with a structural formula shown in the formula I or a pharmaceutically acceptable salt, ester or solvate of the compound with the structural formula shown in the formula I, wherein R1 is H, OCH3, OCH2CH3, Cl, Br, CF3, NO2 or a linear alkyl group with 1 to 5 carbon atoms, R2 is H, OCH3, OCH2CH3, Cl, Br, CF3, NO2 or a linear alkyl group with 1 to 5 carbon atoms, R3 is H, OCH3, OCH2CH3, Cl, Br, CF3, NO2 or a linear alkyl group with 1 to 5 carbon atoms, and n = 1, 2, 3 or 4, the advantages are that the compound can effectively inhibit the activity of DNA topoisomerases, inhibits the proliferation of eukaryotic tumor cells, and prevents and / or treats tumors.
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Paragraph 0021-0022; 0039-0040
(2019/11/14)
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- Synthesis and biological study of acridine-based imidazolium salts
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A new series of acridine based imidazolium salts was synthesized and evaluated for in vitro cytotoxicity against human cancer cell lines by an MTT assay. The synthesis applied a coupling of imidazoles with 9-chloroacridines, which originated from an Ullmann condensation of a 2-chloro-benzoic acid with an aniline. The target compounds were obtained in high yields. The DPPH assay indicated considerable antioxidant activity for target compounds with simple and short alkyl chains on the imidazole, while increasing chain length and the introduction of an additional π-electron system in most cases reduced the activity. All compounds exhibited low biotoxicity against non-cancerous cell lines, whereas a few compounds showed promising anticancer activity. Unlike for the reference drugs Tamoxifen and Paclitaxel, the anticancer activity of acridine imidazolium ions is specific for only selected cancer types. Reasonable fluorescent behaviour of the products provide potential for visualization of the distribution of active drugs in tissue.
- Sharhan, Olla,Heidelberg, Thorsten,Hashim, Najiahah Mohd,Salman, Abbas Abdulameer,Ali, Hapipah Mohd,Jayash, Soher Nagi
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p. 38995 - 39004
(2018/12/02)
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- With anti-tumor activity of the acridine - 1, 3, 4 - oxdiazole compound and its preparation and use
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The present invention discloses an acridine-1,3,4-oxadiazole compound having anti-tumor activity, a preparation method and uses thereof, wherein the structural formula is as the follow. According to the present invention, the acridine-1,3,4-oxadiazole com
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Paragraph 0008; 0021
(2017/06/29)
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- Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy
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PARP-1 could repair the DNA damages induced by Topo inhibitors, therefore inhibiting Topo and PARP-1 simultaneously might be able to overcome resistance and improve outcomes. In this study a series of 4-amidobenzimidazole acridines were designed and synthesized as dual Topo and PARP-1 inhibitors. Compound 11l displayed good inhibitory activities against Topo and PARP-1, as well as significantly inhibited cancer cells proliferation. Further mechanistic evaluations indicated that 11l treatment in MCF-7 cells induced accumulated DNA double-strand breaks, prompted remarkable apoptosis, and caused prominent G0/G1 cell cycle arrest. Moreover, 11l greatly suppressed tumor growth in mice, and displayed favorable metabolic properties in liver microsomes. Our study suggested that single agents inhibiting Topo and PARP concurrently might be an alternative for cancer therapy and 11l represented a potential lead compound for development of antitumor agents.
- Yuan, Zigao,Chen, Shaopeng,Chen, Changjun,Chen, Jiwei,Chen, Chengken,Dai, Qiuzi,Gao, Chunmei,Jiang, Yuyang
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p. 1135 - 1146
(2017/08/02)
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- Application of 2-methoxy-9-acridine benzamido thiourea in preparation of acetylcholinesterase inhibitor
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The invention discloses an application of 2-methoxy-9-acridine benzamido thiourea in preparation of an acetylcholinesterase inhibitor. The constitutional formula (I) of 2-methoxy-9-acridine benzamido thiourea is as shown in the specification. The 2-methox
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Paragraph 0031; 0039; 0040
(2016/10/10)
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- Application of 2-methoxy-9-acridine(4-methoxybenzamido) thiourea to preparing of acetylcholin esterase inhibitor
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The invention discloses an application of 2-methoxy-9-acridine(4-methoxybenzamido) thiourea to preparing of an acetylcholin esterase inhibitor. The structural formula of the 2-methoxy-9-acridine(4-methoxybenzamido)thiourea is shown as the formula (I). The
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Paragraph 0032; 0033; 0040
(2016/10/20)
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- Acridine -1, 2, 4-triazole-5-thione compounds and its preparation method and application
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The invention discloses an acridine-1,2,4-triazole-5-thioketone compound and a preparation method and applications of the acridine-1,2,4-triazole-5-thioketone compound. The preparation method of the compound comprises the following steps: 1) by taking an
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Paragraph 0011; 0031
(2017/02/24)
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- Acridine -1, 2, 3-triazole compound and its preparation method and application
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The invention discloses an acridine-1, 2, 3-triazole type compound and a preparation method and application thereof. The preparation method of the acridine-1, 2, 3-triazole type compound comprises the following steps: 1) performing ullmann reaction by tak
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Paragraph 0023; 0026
(2017/02/24)
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- An acridine mercapto-tetrazole compound and its preparation and use
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The present invention discloses an acridine mercaptotetrazole derivative, a preparation method and uses thereof, wherein the acridine mercaptotetrazole derivative has the structure formula represented in the instruction. According to the present invention
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0027
(2017/03/08)
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- Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents
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The discovery of new effective DNA-targeted antitumor agent is needed because of their clinical significance. As acridines can intercalate into DNA and benzimidazoles have the ability to bind in the DNA minor groove, a series of novel benzimidazole acridine derivatives were designed and synthesized to be new DNA-targeted compounds. MTT assay indicated that most of the synthesized compounds displayed good antiproliferative activity, among which compound 8l demonstrated the highest activity against both K562 and HepG-2 cells. Further experiments showed that 8l displayed good DNA-binding capability and inhibited topoisomerase I activity. Moreover, compound 8l could induce apoptosis in K562 cell lines through mitochondrial pathway. These data suggested that compound 8l might be potential as new DNA-binding and apoptosis-inducing antitumor agents.
- Gao, Chunmei,Li, Bin,Zhang, Bin,Sun, Qinsheng,Li, Lulu,Li, Xi,Chen, Changjun,Tan, Chunyan,Liu, Hongxia,Jiang, Yuyang
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supporting information
p. 1800 - 1807
(2015/03/30)
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- A rapid, chromatography-free route to substituted acridine-isoalloxazine conjugates under microwave irradiation
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Microwave irradiation was applied to a sequence of condensation reactions from readily available 9-chloroacridines to provide a range of novel acridine-isoalloxazine conjugates. The combination of these two moieties, both of biological interest, was achieved by a chromatography-free route.
- Johns, Stephen C.,Crouch, Laurie L.E.,Grieve, Stephen,Maloney, Holly L.,Peczkowski, Gary R.,Jones, Allison E.,Sharp, Duncan,Smith, Robert B.
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supporting information
p. 3308 - 3311
(2014/06/09)
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- Synthesis and preliminary biological evaluation of polyamine-aniline acridines as P-glycoprotein inhibitors
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We have synthesized a series of polyamine-based anilinoacridine derivatives. The preliminary biological evaluation indicated that the 9-anilinoacridine-polyamine derivatives had low or insignificant in vitro cytotoxicity against K562 cell line and K562/ADM, the drug-resistant cell line. However, the evaluation for P-gp modulation showed that they held potent P-gp inhibitory ability. Among them, the effect of compound 7c on P-gp was even greater than that of Verapamil, the known P-gp modulator. The results suggest that 9-anilinoacridine-polyamine derivatives can be employed as effective P-gp modulators.
- Wang, Jianhong,Cheng, Pengfei,Luo, Tianwei,Wang, Zhaoyi,Zhang, Yahong,Zhao, Jin
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p. 506 - 511
(2014/06/23)
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- Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents
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Acridine derivatives have been explored as DNA-binding anticancer agents. Some derivatives show undesired pharmacokinetic properties and new derivatives need to be explored. In this work, a series of novel acridine analogues were synthesized by modifying previously unexplored linkers between the acridine and benzene groups and their antiproliferative activity and the DNA-binding ability were evaluated. Among these derivatives, compound 5c demonstrated DNA-binding capability and topoisomerase I inhibitory activity. In K562 cell lines, 5c induced apoptosis through mitochondria-dependent intrinsic pathways. These data suggested that compound 5c and other acridine derivatives with modified linkers between the acridine and benzene groups might be potent DNA-binding agents.
- Lang, Xuliang,Li, Lulu,Chen, Yuzong,Sun, Qinsheng,Wu, Qin,Liu, Feng,Tan, Chunyan,Liu, Hongxia,Gao, Chunmei,Jiang, Yuyang
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supporting information
p. 4170 - 4177
(2013/07/27)
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- Synthesis, structure-activity relationship and biological activity of acridine derivatives as potent mdr-reversing agents
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Multidrug resistance (MDR) mediated by P-glycoprotein is one of the best characterized transporter-mediated barriers to successful cancer chemotherapy. In an attempt to find MDR-reversing agents, a series of novel acridine derivatives were synthesized and evaluated for their in vitro antiproliferative activities against K562 and K562/ADM cells. Some of these compounds showed superior MDR-reversing activities than Amsacrine, the reference compound. Structureactivity relationships (SAR) of these compounds indicated that the N, N-diethylamine moiety had an affect on the in vitro antiproliferative activity. Interestingly, the compounds bearing N, N-diethylamine moiety showed higher growthinhibitory activity against K562/ADM cells than K562 cells. The high duplex DNA binding affinity and inhibition of topoisomerase of these acridine compounds are maintained which were confirmed by fluorescent quenching and DNA topoisomerase II cleavage assay, respectively. Moreover, several compounds were examined for their ability to increase the accumulation of rhodamine 123 in K562 and K562/ADM cells, and the result suggested that they may be inhibitors for P-glycoprotein. Our study suggested that acridine framework is a potentially interesting scaffold for developing novel MDR-reversing agents.
- Wang, Jianhong,Luo, Tianwei,Li, Shaobin,Zhhang, Yahong,Wang, Chaojie,Zhao, Jin
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p. 4070 - 4079
(2013/12/04)
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- Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors
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Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure-activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 50 400 nM) with a 5.4-fold selectivity over haspin was also identified.
- Cuny, Gregory D.,Robin, Maxime,Ulyanova, Natalia P.,Patnaik, Debasis,Pique, Valerie,Casano, Gilles,Liu, Ji-Feng,Lin, Xiangjie,Xian, Jun,Glicksman, Marcie A.,Stein, Ross L.,Higgins, Jonathan M.G.
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scheme or table
p. 3491 - 3494
(2010/08/21)
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- Convenient access to substituted acridines by a Buchwald-Hartwig amination
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A convenient, high yield procedure for the synthesis of anthranilic acids carrying a variety of different substituents as well as their straightforward transformation into the corresponding 9-chloroacridines could be established by using modified Buchwald-Hartwig amination conditions.
- Csuk, René,Barthel, Alexander,Raschke, Christian
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p. 5737 - 5750
(2007/10/03)
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- Synthesis of new atropisomers derived from methoxychloroacridine. Preparation of enantiomerically pure (aR)-(-)-2,2′-dihydroxy-9,9′-biacridine
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New biacridinyl atropisomers were obtained from symmetric ligand 2,2′-dihydroxy-9,9′-biacridine (4), prepared from 9-chloro-2-methoxyacridine. Alternative O-acylation and alkylation led to different polycycles and to a biacridinyl crown ether. The molecular structures of 2,2′-di(p-chlorobenzoyloxy)-9,9′-biacridinyl (5) and (9,9′-bisacridinyl)-2,2′-dihydroxy-bis-(camphanate) ester (13) were solved by X-Ray crystallography, showing a 'scissor-like' host conformation and guest inclusion of chloroform and acetonitrile. The determination of X-Ray structure of one diastereomer (13) allows to assign the absolute configuration of enantiomerically recovered (aR)-(-)-2,2′-dihydroxy-9,9′-biacridinyl.
- Tuan Lormier, Anh,Boyer, Gérard,Faure, Robert,Pierre Galy, Jean
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p. 449 - 463
(2007/10/03)
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- Frameshift mutagenicity and DNA intercalation of 9-amino-2-hydroxyacridine, a rat liver S9 metabolite of 9-aminoacridine
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9-Amino-2-hydroxyacridine, a rat liver S9 metabolite of 9-aminoacridine (9-AA), was synthesized, and found to have lower frameshift mutagenicity and stronger DNA binding affinity than 9-AA.
- Tomosaka, Hideyuki,Anzai, Kentaro,Hasegawa, Eietsu,Horigome, Tsuneyoshi,Omata, Saburo
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p. 714 - 716
(2007/10/03)
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