Azaflavones compared to flavones as ligands to the benzodiazepine binding site of brain GABA(A) receptors.
A series of azaflavone derivatives and analogues were prepared and evaluated for their affinity to the benzodiazepine binding site of the GABA(A) receptor, and compared to their flavone counterparts. Three of the compounds, the azaflavones 9 and 12 as well as the new flavone 13, were also assayed on GABA(A) receptor subtypes (alpha(1)beta(3)gamma(2s), alpha(2)beta(3)gamma(2s), alpha(4)beta(3)gamma(2s) and alpha(5)beta(3)gamma(2s)), displaying nanomolar affinities as well as selectivity for alpha1- versus alpha2- and alpha3-containing receptors by a factor of between 14 and 26.
Department of Organic Chemistry, Lund University, SE-221 00 Lund, Sweden.
Jakob
J
Nilsson
Elsebet Østergaard
EØ
Nielsen
Tommy
T
Liljefors
Mogens
M
Nielsen
Olov
O
Sterner
D000818:Animals; D001372:Aza Compounds / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D047309:Flavones / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D001372:Aza Compounds; D047309:Flavones; D008024:Ligands; D011963:Receptors, GABA-A; D001569:Benzodiazepines