Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase

Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT).

The enzyme catechol O-methyltransferase (COMT) catalyzes the Me group transfer from the cofactor S-adenosylmethionine (SAM) to the hydroxy group of catechol substrates. Potential bisubstrate inhibitors of COMT were developed by structure-based design and synthesized. The compounds were tested for in vitro inhibitory activity against COMT obtained from rat liver, and the inhibition kinetics were...

Amido-3-hydroxypyridin-4-ones as iron(III) ligands.

The synthesis and physicochemical properties of a range of 2- and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pK(a) values than 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pK(a) values of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatica...

Synthesis and biological evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents

A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (K(part)) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC(50) of HPOs was determined using MTT assay. Among these ligands, compound 4e (K(part)=5.02) with an IC(50) of 30 μM and 4f (K(part)=0.1) with an IC(50) of 700 μ...

synthesis and cytotoxic evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents

Nitrocatechol derivatives as inhibitors of catechol-O-methyltransferase.

Catechol-0-methyltransferase (EC 2.1.1.6; COMT) catalyses Sadenosylmethionine-dependent methylation of a variety of catechols and plays a role in terminating the activities of the catecholamine neurotransmitters dopamine and noradrenaline. Two isoenzymes, the soluble and membrane-bound forms (S-COMT and MB-COMT) are present in most tissues and although the former is more abundant, their differe...