19147-02-5Relevant academic research and scientific papers
Synthesis and cytotoxic evaluation of novel indenoisoquinoline-propan-2-ol hybrids
Thi, Tham Pham,Decuyper, Lena,Quang, Tan Luc,The, Chinh Pham,Dang Thi, Tuyet Anh,Nguyen, Ha Thanh,Le Nhat, Thuy Giang,Thanh, Tra Nguyen,Thi, Phuong Hoang,D'Hooghe, Matthias,Van Nguyen, Tuyen
, p. 466 - 471 (2016)
The synthesis of N-substituted indenoisoquinolines was performed by applying a two-step condensation between 2-carboxybenzaldehyde and phthalide, followed by treatment with various primary amines. N-allylindenoisoquinoline was subsequently selected as a s
Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: Versatile intermediates for the design and synthesis of topoisomerase I inhibitors
Morrell, Andrew,Antony, Smitha,Kohlhagen, Glenda,Pommier, Yves,Cushman, Mark
, p. 1846 - 1849 (2006)
A method has been developed that relies on a two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes to provide benz[d]indeno[1,2-b] pyran-5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary amine allows ra
Iridium(iii) complexes as mitochondrial topoisomerase inhibitors against cisplatin-resistant cancer cells
Chao, Hui,Chen, Yu,Guan, Ruilin,He, Liting,Ji, Liangnian,Wang, Lili,Xiong, Kai
supporting information, p. 8308 - 8311 (2021/08/25)
Herein, we developed the first metal-based mitochondrial topoisomerase inhibitors to achieve an effective therapeutic outcome for the therapy of cisplatin-resistant tumour cells. This journal is
SYNTHESIS AND USE OF DUAL TYROSYL-DNA PHOSPHODIESTERASE I (TDP1)- TOPOISOMERASE I (TOP1) INHIBITORS
-
Paragraph 0128, (2014/02/15)
The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.
Synthesis and biological evaluation of the first dual tyrosyl-DNA phosphodiesterase i (Tdp1)-topoisomerase i (Top1) inhibitors
Nguyen, Trung Xuan,Morrell, Andrew,Conda-Sheridan, Martin,Marchand, Christophe,Agama, Keli,Bermingam, Alun,Stephen, Andrew G.,Chergui, Adel,Naumova, Alena,Fisher, Robert,O'Keefe, Barry R.,Pommier, Yves,Cushman, Mark
experimental part, p. 4457 - 4478 (2012/08/07)
Substances with dual tyrosyl-DNA phosphodiesterase I-topoisomerase I inhibitory activity in one low molecular weight compound would constitute a unique class of anticancer agents that could potentially have significant advantages over drugs that work against the individual enzymes. The present study demonstrates the successful synthesis and evaluation of the first dual Top1-Tdp1 inhibitors, which are based on the indenoisoquinoline chemotype. One bis(indenoisoquinoline) had significant activity against human Tdp1 (IC 50 = 1.52 ± 0.05 μM), and it was also equipotent to camptothecin as a Top1 inhibitor. Significant insights into enzyme-drug interactions were gained via structure-activity relationship studies of the series. The present results also document the failure of the previously reported sulfonyl ester pharmacophore to confer Tdp1 inhibition in this indenoisoquinoline class of inhibitors even though it was demonstrated to work well for the steroid NSC 88915 (7). The current study will facilitate future efforts to optimize dual Top1-Tdp1 inhibitors.
Indeno[1,2-c]isoquinolin-5,11-diones conjugated to amino acids: Synthesis, cytotoxicity, DNA interaction, and topoisomerase II inhibition properties
Ahn, Gang,Lansiaux, Amélie,Goossens, Jean-Fran?ois,Bailly, Christian,Baldeyrou, Brigitte,Schifano-Faux, Nadège,Grandclaudon, Pierre,Couture, Axel,Ryckebusch, Adina
experimental part, p. 8119 - 8133 (2011/01/13)
Three series of indeno[1,2-c]isoquinolin-5,11-dione-amino acid conjugates were designed and synthesized. Amino acids were connected to the tetracycle through linkers with lengths of n = 2 and 3 atoms using ester (series I), amide (series II), and secondary amine (series III) functions. DNA binding was evaluated by thermal denaturation and fluorescence measurements. Lysine and arginine substituted derivatives with n = 3 provided the highest DNA binding. Arginine derivative 32 (n = 2, series II) and glycine derivative 34 (n = 2, series III) displayed high topoisomerase II inhibition. Incrementing the length of the N-6 side chain from two to three methylene units provided a significant increase in DNA affinity but a substantial loss in topoisomerase II inhibition. The most cytotoxic compounds toward HL60 leukemia cells were 19, 33, and 34 displaying micromolar IC50 values. When tested with the topoisomerase II-mutated HL60/MX2 cell line, little variation of IC50 values was found, suggesting that topoisomerase II might not be the main target of these compounds and that additional targets could be involved.
N-SUBSTITUTED INDENOISOQUINOLINES AND SYNTHESES THEREOF
-
Page/Page column 20; 35, (2008/06/13)
N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for
Hypolipidemic Activity of Indan-1,3-dione Derivatives in Rodents
Murthy, A. R.,Wyrick, S. D.,Hall, I. H.
, p. 1591 - 1596 (2007/10/02)
A series of 2-substituted indan-1,3-dione derivatives, including alkyl (C-1-C-5), mono- and disubstituted phenyl, and other 2-aryl derivatives, were tested for hypolipidemic activity of CF1 male mice at 20 mg/kg per day.These derivatives reduced both serum cholesterol and triglycerides after 16 days of administration intraperitoneally. 2-(4-Methoxyphenyl)indan-1,3-dione was one of the more active compounds with 41percent reduction of serum cholesterol and 58percent reduction of serum triglyceride levels on day 16.This activity was confirmed in the rat after oral administration. 2-(2-Methylphenyl)- and 2-(4-chlorophenyl)indan-1,3-dione were effective in reducing serum triglyceride levels 58percent and 53percent, respectively, in mice.Serum cholesterol on day 16 was effectively reduced 46percent by 2-(2,4-dimethylphenyl)indan-1,3-dione.The indan-1,3-dione derivatives were more effective than clofibrate in lowering lipid levels in mice.A more detailed study on the effects of 2-(4-methoxyphenyl)indan-1,3-dione demonstrated that key enzymes in the de novo synthesis of lipids were inhibited by the drug lowering tissue levels of lipids but raising those in the feces.The alterations in lipid content of rat lipoprotein fractions by the drug appeared favorable.
