95911-71-0Relevant academic research and scientific papers
The rearrangement of tosylated flavones to 1′-(alkylamino)aurones with primary amines
Kandioller, Wolfgang,Kubanik, Mario,Bytzek, Anna K.,Jakupec, Michael A.,Roller, Alexander,Keppler, Bernhard K.,Hartinger, Christian G.
, p. 8953 - 8959 (2015/11/02)
A rearrangement of 3-tosylflavone to the corresponding 1′-(alkylamino)aurone proceeds under mild conditions in the presence of primary amines in high yields. The reaction is applicable to different substituted 3-tosylflavones and alkyl amines and the respective aurones were isolated as a mixture of E/Z isomers. Further conversion of 1′-(methylamino)aurone to the corresponding thionated compound was performed by reaction with Lawesson's reagent and only the E isomer was obtained. This observation can be explained by the weaker exocyclic double bond, which facilitates rotation and the formation of the thermodynamically preferred E form. The characterization, preliminary biological investigations of the synthesized compounds and lipophilicity studies are discussed.
Pharmacophore model of the quercetin binding site of the SIRT6 protein
Ravichandran,Singh,Donnelly,Migliore,Johnson,Fishwick,Luke,Martin,Maudsley,Fugmann,Moaddel
, p. 38 - 46 (2014/03/21)
SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors,
Superior anticancer activity of halogenated chalcones and flavonols over the natural flavonol quercetin
Dias, Tatiana A.,Duarte, Cecília L.,Lima, Cristovao F.,Proen?a, M. Fernanda,Pereira-Wilson, Cristina
, p. 500 - 510 (2013/10/01)
A series of chalcone and flavonol derivatives were synthesized in good yield by an eco-friendly approach. A pharmacological evaluation was performed with the human colorectal carcinoma cell line HCT116 and revealed that the anticancer activity of flavonols was higher when compared with that of the respective chalcone precursors. The antiproliferative activity of halogenated derivatives increases as the substituent in the 3- or 4-positon of the B-ring goes from F to Cl and to Br. In addition, halogens in position 3 enhance anticancer activity in chalcones whereas for flavonol derivatives the best performance was registered for the 4-substituted derivatives. Flow cytometry analysis showed that compounds 3p and 4o induced cell cycle arrest and apoptosis as demonstrated by increased S, G2/M and sub-G1 phases. These data were corroborated by western blot and fluorescence microscopy analysis. In summary, halogenated chalcones and flavonols were successfully prepared and presented high anticancer activity as shown by their cell growth and cell cycle inhibitory potential against HCT116 cells, superior to that of quercetin, used as a positive control.
Understanding the cardioprotective effects of flavonols: Discovery of relaxant flavonols without antioxidant activity
Cheng, Xue Qin,Chen, Xingqiang,Hughes, Richard A.,Williams, Spencer J.,Woodman, Owen L.
, p. 1874 - 1884 (2008/12/21)
3′,4′-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that can reduce injury after myocardial ischemia and reperfusion and thus is a promising small molecule for the treatment of cardiovascular disease. Like all vasoactive flavonols reported to date, DiOHF is both relaxant and antioxidant, hindering investigation of the relative contribution of each activity for the prevention of reperfusion injury. This study investigates structure-activity relationships of variations at the 3′ and 4′ positions of the B ring of DiOHF and vasorelaxant and antioxidant activities. Relaxation of rat isolated aortic rings precontracted with KCl revealed that the most active flavonols were those with a 4′-hydroxyl group, with the opening of potassium channels as a possible contributing mechanism. For the antioxidant activity, with the exception of DiOHF, none of the flavonols investigated were able to significantly scavenge superoxide radical, and none of the three most potent vasorelaxant flavonols could prevent oxidant-induced endothelial dysfunction. The discovery of single-acting vasorelaxant flavonols without antioxidant activity, in particular 4′-hydroxy-3′-methoxyflavonol, will assist in investigating the mechanism of flavonol-induced cardioprotection.
Antimicrobial effects of novel siderophores linked to β-lactam antibiotics
Kline,Fromhold,McKennon,Cai,Treiberg,Ihle,Sherman,Schwan,Hickey,Warrener,Witte,Brody,Goltry,Barker,Anderson,Tanaka,Shawar,Nguyen,Langhorne,Bigelow,Embuscado,Naeemi
, p. 73 - 93 (2007/10/03)
As a strategy to increase the penetration of antibiotic drugs through the outer membrane of Gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-β-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities, suggesting that multiple factors influenced the intracellular concentration of the drugs. (C) 2000 Elsevier Science Ltd.
