Synthesis and cytotoxic activity of novel 11-methyl-6H-pyrido[4,3-b]carbazole derivatives linked to amine, N-methylurea, and N-methyl-N-nitrosourea moieties with various types of carbamoyl tethers at the C-5 atom
作者： Asako Kato , Yusuke Nagatsuka , Tomokazu Hiratsuka , Satoko Kiuchi , Yoko Iwase
DOI: 10.1016/J.TET.2016.05.068
关键词: Conjugated system 、 Carbazole 、 Amine gas treating 、 Stereochemistry 、 HeLa 、 Cytotoxic T cell 、 Alkyl 、 Chloride 、 Chemistry 、 IC50 、 Organic chemistry 、 Biochemistry 、 Drug discovery
摘要: Abstract Thirty-five types of novel pyridocarbazoles (5-(N-alkyl)carbamoyl-11-methyl-6H-pyrido[4,3-b]carbazoles and 5-(N-alkyl)carbamoyl-2,11-dimethyl-6H-pyrido[4,3-b]carbazol-2-ium chloride derivatives), that were conjugated with amine, N-methylurea, N-methyl-N-nitrosourea moieties through alkyl-, oxyalkyl-, iminoalkylcarbamoyl linkers, synthesized by a series reactions methyl 11-methyl-6H-pyrido[4,3-b]carbazole-5-carboxylates polymethylenediamine (n=2–5), p-nitrophenyl N-methylcarbamate, N-methyl-N-nitrosocarbamate in high yields, their cytotoxic activities evaluated against Sarcoma-180, NIH3T3, HeLa S-3, L1210 cell lines. These compounds exhibited potent activity (IC50=1.6–50 μM) odd-even alternation effect. 9-Methoxy-2,11-dimethyl-5-((2-(3-methyl-3-nitrosoureido)ethyl)carbamoyl)-6H-pyrido[4,3-b]carbazol-2-ium the most (IC50=0.15 μM) cell selectivity S-3. Some un-charged 5-(N-alkyl)carbamoyl-6H-pyrido[4,3-b]carbazole derivatives, which amine dimethylene spacer, also (IC50=0.43–2.4 μM) remarkable as well ellipticine, 9-hydroxyellipticine, starting ester pyridocarbazole-5-carboxylate (IC50=0.30–2.2 μM).
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sci-hub.se 参考文章(64)
G Meunier, B Meunier, Peroxidase-catalyzed O-demethylation reactions. Quinone-imine formation from 9-methoxyellipticine derivatives. Journal of Biological Chemistry. ,vol. 260, pp. 10576- 10582 ,(1985) , 10.1016/S0021-9258(19)85124-4
Kurt W. Kohn, Charles A. Friedman, Daniel Glaubiger, Michael J. Waring, Intercalative binding of ellipticine to DNA. Cancer Research. ,vol. 35, pp. 71- 76 ,(1975)
Leming M. Shi, Timothy G. Myers, Yi Fan, Patrick M. O’Connor, Kenneth D. Paull, Stephen H. Friend, John N. Weinstein, Mining the National Cancer Institute Anticancer Drug Discovery Database: cluster analysis of ellipticine analogs with p53-inverse and central nervous system-selective patterns of activity. Molecular Pharmacology. ,vol. 53, pp. 241- 251 ,(1998) , 10.1124/MOL.53.2.241
Claude Paoletti, Jacques Paoletti, Jean Belehradek, Annette K. Larsen, Uptake, Cytofluorescence, and Cytotoxicity of Oxazolopyridocarbazoles (Amino Acid-Ellipticine Conjugates) in Murine Sarcoma Cells Cancer Research. ,vol. 46, pp. 5236- 5240 ,(1986)
P Krishnamoorthy, P Sathyadevi, Alan H Cowley, Rachel R Butorac, N Dharmaraj, None, Evaluation of DNA binding, DNA cleavage, protein binding and in vitro cytotoxic activities of bivalent transition metal hydrazone complexes European Journal of Medicinal Chemistry. ,vol. 46, pp. 3376- 3387 ,(2011) , 10.1016/J.EJMECH.2011.05.001
Ching-Yuan Liu, Paul Knochel, Preparation of polyfunctional aryl azides from aryl triazenes. A new synthesis of ellipticine, 9-methoxyellipticine, isoellipticine, and 7-carbethoxyisoellipticine. Journal of Organic Chemistry. ,vol. 72, pp. 7106- 7115 ,(2007) , 10.1021/JO070774Z
J. W. Mackley, D. A. Carlson, J. F. Butler, Identification of the cuticular hydrocarbons of the horn fly and assays for attraction. Journal of Chemical Ecology. ,vol. 7, pp. 669- 683 ,(1981) , 10.1007/BF00990300
Jean-Yves Charcosset, Alain Jacquemin-Sablon, Jean-Bernard Le Pecq, Effect of membrane potential on the cellular uptake of 2-N-methyl-ellipticinium by L1210 cells Biochemical Pharmacology. ,vol. 33, pp. 2271- 2275 ,(1984) , 10.1016/0006-2952(84)90666-X
Pier Lucio Anelli, Fernando Montanari, Silvio Quici, Synthesis of [H+.cntnd.(1.1.1)]X- cryptates assisted by intramolecular hydrogen bonding The Journal of Organic Chemistry. ,vol. 50, pp. 3453- 3457 ,(1985) , 10.1021/JO00219A007
Reiko Ikeda, Masaki Kurosawa, Takazumi Okabayashi, Ayako Takei, Masamichi Yoshiwara, Tadashi Kumakura, Norio Sakai, Osamu Funatsu, Akinori Morita, Masahiko Ikekita, Yumi Nakaike, Takeo Konakahara, 3-(3-Phenoxybenzyl)amino-β-carboline: a novel antitumor drug targeting α-tubulin. Bioorganic & Medicinal Chemistry Letters. ,vol. 21, pp. 4784- 4787 ,(2011) , 10.1016/J.BMCL.2011.06.061