116289-25-9Relevant academic research and scientific papers
Structure-function relationships in aminoquinolines: Effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of β- hematin formation, and antiplasmodial activity
Egan, Timothy J.,Hunter, Roger,Kaschula, Catherine H.,Marques, Helder M.,Misplon, Ashley,Walden, Jason
, p. 283 - 291 (2000)
Comparison of 19 aminoquinolines supports the hypothesis that chloroquine and related antimalarials act by complexing ferriprotoporphyrin IX (Fe(III)PPIX), inhibiting its conversion to β-hematin (hemozoin) and hence its detoxification. The study suggests that a basic amino side chain is also essential for antiplasmodial activity. 2- And 4-aminoquinolines are unique in their strong affinity for Fe(III)PPIX, and attachment of side chains to the amino group has relatively little influence on the strength of complex formation. Association with Fe(III)PPIX is necessary, but not sufficient, for inhibiting β-hematin formation. Presence of a 7-chloro group in the 4-aminoquinoline ring is a requirement for β-hematin inhibitory activity, and this is also unaffected by side chains attached to the amino group. In turn, β-hematin inhibitory activity is necessary, but not sufficient, for antiplasmodial activity as the presence of an aminoalkyl group attached to the 4-amino-7-chloroquinoline template is essential for strong activity. We thus propose that the 4-aminoquinoline nucleus of chloroquine and related antimalarials is responsible for complexing Fe(III)PPIX, the 7-chloro group is required for inhibition of β-hematin formation, and the basic amino side chain is required for drug accumulation in the food vacuole of the parasite.
Rational Design of Bisubstrate-Type Analogues as Inhibitors of DNA Methyltransferases in Cancer Cells
Halby, Ludovic,Menon, Yoann,Rilova, Elodie,Pechalrieu, Dany,Masson, Véronique,Faux, Celine,Bouhlel, Mohamed Amine,David-Cordonnier, Marie-Hélène,Novosad, Natacha,Aussagues, Yannick,Samson, Arnaud,Lacroix, Laurent,Ausseil, Fréderic,Fleury, Laurence,Guianvarc'H, Dominique,Ferroud, Clotilde,Arimondo, Paola B.
, p. 4665 - 4679 (2017)
Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline. The most potent inhibitors induced demethylation of CDKN2A promoter in colon carcinoma HCT116 cells and its reactivation after 7 days of treatment. Furthermore, in a leukemia cell model system, we found a correlation between demethylation of the promoter induced by the treatment, chromatin opening at the promoter, and the reactivation of a reporter gene.
Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells
Mendes, Eduarda,Cadoni, Enrico,Carneiro, Filipa,Afonso, Marta B.,Brito, Hugo,Lavrado, Jo?o,dos Santos, Daniel J. V. A.,Vítor, Jorge B.,Neidle, Stephen,Rodrigues, Cecília M. P.,Paulo, Alexandra
, p. 1325 - 1328 (2019)
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline
Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3
Oukoloff, Killian,Coquelle, Nicolas,Bartolini, Manuela,Naldi, Marina,Le Guevel, Rémy,Bach, Stéphane,Josselin, Béatrice,Ruchaud, Sandrine,Catto, Marco,Pisani, Leonardo,Denora, Nunzio,Iacobazzi, Rosa Maria,Silman, Israel,Sussman, Joel L.,Buron, Frédéric,Colletier, Jacques-Philippe,Jean, Ludovic,Routier, Sylvain,Renard, Pierre-Yves
supporting information, p. 58 - 77 (2019/02/25)
Both cholinesterases (AChE and BChE) and kinases, such as GSK-3α/β, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3α/β (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3α/β. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp.
SUBSTITUTED QUINAZOLINE DERIVATIVES AS DNA METHYLTRANSFERASE INHIBITORS
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Page/Page column 50; 51, (2016/10/11)
The present invention relates to compounds of the following formula (I) and pharmaceutically acceptable salts and solvates thereof, their methods of preparation, their use as a drug, notably in the treatment of cancer, and pharmaceutical compositions containing such compounds.
QUINAZOLINE DERIVATIVES AND THEIR USE AS DNA METHYLTRANSFERASE INHIBITORS
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Page/Page column 38, (2015/04/15)
The present invention relates to compounds of the following formula (I): and pharmaceutically acceptable salts and solvates thereof, their methods of preparation, their use as a drug, notably in the treatment of cancer, and pharmaceutical compositions containing such compounds.
Synthesis and in vitro antitubercular activity of a series of quinoline derivatives
de Souza, Marcus V.N.,Pais, Karla C.,Kaiser, Carlos R.,Peralta, Monica A.,de L. Ferreira, Marcelle,Lourenco, Maria C.S.
experimental part, p. 1474 - 1480 (2009/08/15)
A series of 33 quinoline derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds 5e and 5f exhibited a significant activity at 6.25 and 3.12 μg/mL, respectively, when compared with first line drugs such as ethambutol and could be a good starting point to develop new lead compounds in the fight against multi-drug resistant tuberculosis.
Dihydro-1,4-oxazino(2,3-C)quinolines
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, (2008/06/13)
There are disclosed novel compounds of the formula STR1 where X is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, nitro or trifluoromethyl; R1 is hydrogen or loweralkyl; R2 is hydrogen, loweralkyl, arylloweralkyl or --(CH2
