63450-45-3Relevant academic research and scientific papers
Benzoflavone derivatives as potent antihyperuricemic agents
Singh, Jatinder V.,Mal, Gurbachan,Kaur, Gurleen,Gupta, Manish K.,Singh, Amritpal,Nepali, Kunal,Singh, Harbinder,Sharma, Sahil,Bedi, S. Preet Mohinder
, p. 128 - 147 (2019/01/30)
Two series of benzoflavone derivatives were rationally designed, synthesized and evaluated for their xanthine oxidase (XO) inhibitory potential. Among both series, eight compounds (NF-2, NF-4, NF-9, NF-12, NF-16, NF-25, NF-28, and NF-32) were found to exert significant XO inhibition with IC50 values lower than 10 μM. Enzyme kinetic studies revealed that the most potent benzoflavone derivatives (NF-4 and NF-28) are mixed type inhibitors of the XO enzyme. Molecular modeling studies were also performed to investigate the binding interactions of these molecules (NF-4 and NF-28) with the amino acid residues present in the active site of the enzyme. Docking results confirmed that their favorable binding conformations in the active site of XO can completely block the catalytic activity of the enzyme. Benzoflavone derivatives exhibiting potent XO enzyme inhibition also showed promising results in a hyperuricemic mice model when tested in vivo.
Rh(III)-Catalyzed Aldehydic C?H Functionalization Reaction between Salicylaldehydes and Sulfoxonium Ylides
Xu, Guo-Dong,Huang, Kenneth L.,Huang, Zhi-Zhen
supporting information, p. 3318 - 3323 (2019/06/25)
A novel aldehydic C?H functionalization reaction between salicylaldehydes and sulfoxonium ylides has been developed under rhodium(III) catalysis, affording coupling products in moderate to good yields. A plausible mechanism involving aldehydic C(sp2)?H activation by rhodium(III) and rhodium(III) catalyzed carbene insertion is also proposed. It was also found that the aldehydic C?H functionalization followed by dehydrative cyclization was able to produce flavonoids in one-pot. (Figure presented.).
Benzoflavones as cholesterol esterase inhibitors: Synthesis, biological evaluation and docking studies
Singh, Harbinder,Singh, Jatinder Vir,Gupta, Manish K.,Singh, Palwinder,Sharma, Sahil,Nepali, Kunal,Bedi, Preet Mohinder S.
supporting information, p. 850 - 854 (2017/02/12)
A library of forty 7,8-benzoflavone derivatives was synthesized and evaluated for their inhibitory potential against cholesterol esterase (CEase). Among all the synthesized compounds seven benzoflavone derivatives (A-7, A-8, A-10, A-11, A-12, A-13, A-15) exhibited significant inhibition against CEase in in vitro enzymatic assay. Compound A-12 showed the most promising activity with IC50value of 0.78?nM against cholesterol esterase. Enzyme kinetic studies carried out for A-12, revealed its mixed-type inhibition approach. Molecular protein–ligand docking studies were also performed to figure out the key binding interactions of A-12 with the amino acid residues of the enzyme's active site. The A-12 fits well at the catalytic site and is stabilized by hydrophobic interactions. It completely blocks the catalytic assembly of CEase and prevents it to participate in ester hydrolysis mechanism. The favorable binding conformation of A-12 suggests its prevailing role as CEase inhibitor.
Benzoflavone activators of the cystic fibrosis transmembrane conductance regulator: Towards a pharmacophore model for the nucleotide-binding domain
Springsteel, Mark F.,Galietta, Luis J. V.,Ma, Tonghui,By, Kolbot,Berger, Gideon O.,Yang, Hong,Dicus, Christopher W.,Choung, Wonken,Quan, Chao,Shelat, Anang A.,Guy, R. Kiplin,Verkman,Kurth, Mark J.,Nantz, Michael H.
, p. 4113 - 4120 (2007/10/03)
Our previous screen of flavones and related heterocycles for the ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel indicated that UCCF-029, a 7,8-benzoflavone, was a potent activator. In the present study, we describe the synthesis and evaluation, using cell-based assays, of a series of benzoflavone analogues to examine structure-activity relationships and to identify compounds having greater potency for activation of both wild type CFTR and a mutant CFTR (G551D-CFTR) that causes cystic fibrosis in some human subjects. Using UCCF-029 as a structural guide, a panel of 77 flavonoid analogues was prepared. Analysis of the panel in FRT cells indicated that benzannulation of the flavone A-ring at the 7,8-position greatly improved compound activity and potency for several flavonoids. Incorporation of a B-ring pyridyl nitrogen either at the 3- or 4-position also elevated CFTR activity, but the influence of this structural modification was not as uniform as the influence of benzannulation. The most potent new analogue, UCCF-339, activated wild-type CFTR with a Kd of 1.7 μM, which is more active than the previous most potent flavonoid activator of CFTR, apigenin. Several compounds in the benzoflavone panel also activated G551D-CFTR, but none were as active as apigenin. Pharmacophore modeling suggests a common binding mode for the flavones and other known CFTR activators at one of the nucleotide-binding sites, allowing for the rational development of more potent flavone analogues.
Reactions of Carbonyl Compounds in Basic Solutions. Part 11. The Baker-Venkataraman Rearrangement
Bowden, Keith,Chehel-Amiran, Mohsen
, p. 2039 - 2044 (2007/10/02)
The detailed mechanism of the Baker-Venkataraman rearrangement has been studied.The kinetics of the rearrangement of a series of 2-acetylphenyl 3- or 4-substituted benzoates and acetylnaphthyl benzoates catalysed by a basic 'non-nucleophilic' buffer in dimethyl sulphoxide have been measured.Studies of substituent effects, kinetic isotope effects, and acidity function correlations indicate a pathway involving pre-equilibrium formation of the carbanion, followed by rate-determining intramolecular nucleophilic attack.The methanolysis of the 2-acetylphenyl benzoates catalysed by methoxide in methanolic dimethyl sulphoxide has been similary investigated.In this case the pathway appears to involve neighbouring group participation by the ketonic carbonyl group.
