Synthesis and biological evaluation of fused dipyranoquinolinones as inhibitors of acetylcholinesterase with antioxidant properties

Development of potent cholinesterase inhibitors based on a marine pharmacophore

“…The potential of the investigated compounds is further increased by the fact that natural barettin and its analogs are efficient antioxidants 38,39 suggesting that there is potential to tailor this activity into this scaffold to generate multi-target directed ligands (MTDLs) for AD treatment. 63,64 Natural products have been heralded as a particularly promising source for MTDL design 63,65 and our results could be used to accelerate this development.…”

Synthesis and Biological Evaluation of Substituted Fused Dipyranoquinolinones

“…The reactions for the synthesis of the methyl-substituted pyridine moiety of fused pyridocoumarins are presented in Scheme 1. The starting compounds, hydroxyaminocoumarins 1a,b [53,54] and 1c-e [39,55,56] were prepared by the Pd-catalyzed reduction of the corresponding hydroxynitrocoumarins in methanol under an H 2 atmosphere at room temperature [39]. The reaction of 6-amino-7-hydroxycoumarin (1a) with an excess of n-butyl vinyl ether (2) in the presence of a catalytic amount (10%) of I 2 in CH 3 CN under reflux for 1 h resulted in the preparation of 6-hydroxy-8-methyl-3H-pyrano[3,2-f ]quinolin-3-one (3a) (see Supplementary Materials) in a 94% yield (Scheme 1, Table 1, entry 1).…”

“…With the propargyloxy derivatives of fused pyridocoumarins in hand (Scheme 1), the optimal conditions for their cyclization to the corresponding pyran derivatives were investigated using 1,8-dimethyl-6-(prop-2-yn-1-yloxy)-3H-pyrano[3,2-f ]quinolin-3-one (7b) as the model substrate (Table 2). At first, we attempted the cyclization of 7b in the presence of Au/TiO 2 (4 mol%) in DCE under microwave irradiation at 140 • C according to the recently reported synthesis of fused pyranocoumarins [39,47]. The starting compound remained unchanged (Table 2, entry 1).…”

“…The formation of the pyran moiety of fused pyranocoumarins is achieved mainly by the Claisen rearrangement of propargyloxycoumarins followed by cyclization [37] or by the reaction of hydroxycoumarins with α,β-unsaturated aldehydes or ketones [38]. In this paper, we build on our extensive experience in the synthesis of fused pyridocoumarin [39][40][41][42][43][44][45][46] and pyranocoumarin derivatives [47][48][49][50][51][52], and recently published work on fused coumarins with pyridine and pyran moieties [39], and propose the synthesis and biological evaluation of substituted fused pyridopyranocoumarins. We are using new substituted fused pyridocoumarins, which, through the propargyloxy derivatives, are transformed to the title compounds via Au-nanoparticles catalysis.…”

An Overview on the Synthesis of Fused Pyridocoumarins with Biological Interest

“…Very recently, our group synthesized bis-fused pyridopyranocoumarins 128a , b , 131 , 134a , b from the propargylaminocoumarin derivatives 126a , b , 127a , b , 120 , 133a , b in excellent yields under Au-NPs catalyzed cycloisomerization reaction followed by air oxidation [ 108 ]. The propargylaminocoumarins have been synthesized from aminohydroxycoumarins 125a , b and 129 under propargylation with propargyl bromide ( 99 ) or 3-chloro-3-methylbutyne ( 93 ) ( Scheme 28 ).…”