Carmen Picciau

A new series of 3-phenylcoumarins as potent and selective MAO-B inhibitors

6-Methyl-3-phenylcoumarins 3-6 were designed, synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. The synthesis of these new compounds (resveratrol-coumarin hybrids) was carried out with good yield by a Perkin reaction, from the 5-methylsalicylaldehyde and the corresponding phenylacetic acid. They show high selectivity to the MAO-B isoenzyme, with IC(50) values in the nanomolar range. Compound 5 is the most active compound and is several times more potent and selective than the reference compound, R-(-)-deprenyl.

Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors.

A series of 6-methyl-3-phenylcoumarins 3-6 were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. A comparative study between the three possible mono methoxy 3-phenyl derivatives and the p-hydroxy analogue is reported. The synthesis of these new resveratrol-coumarin hybrids was carried out by a Perkin reaction between the 5-methylsalicylaldehyde and the corresponding phenylacetic acids. The p-methoxy substituted compound 3 was hydrolyzed to 6 by a traditional reaction with hydriodic acid. The prepared compounds show high selectivity to the MAO-B isoenzyme, some of them with IC(50) values in the low nanomolar range. Compound 4, with the methoxy group in meta position, is the most active of this series, with an IC(50) against MAO-B of 0.80 nM, and is several times more potent and MAO-B selective than the R-(-)-deprenyl (reference compound).

Synthesis and Vasorelaxant and Platelet Antiaggregatory Activities of a New Series of 6-Halo-3-phenylcoumarins †

A series of 6-halo-3-hydroxyphenylcoumarins (resveratrol-coumarins hybrid derivatives) was synthesized in good yields by a Perkin reaction followed by hydrolysis. The new compounds were evaluated for their vasorelaxant activity in intact rat aorta rings pre-contracted with phenylephrine (PE), as well as for their inhibitory effects on platelet aggregation induced by thrombin in washed human platelets. These compounds concentration-dependently relaxed vascular smooth muscle and some of them showed a platelet antiaggregatory activity that was up to thirty times higher than that shown by trans-resveratrol and some other previously synthesized derivatives.

Synthesis, human monoamine oxidase inhibitory activity and molecular docking studies of 3-heteroarylcoumarin derivatives.

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Series of 3-indolyl and 3-thiophenylcoumarins were synthesized and evaluated as inhibitors of the two human MAO isoforms, hMAO-A and hMAO-B. In general, the derivatives were found to be selective hMAO-B inhibitors with IC(50) values in the nanoMolar (nM) to microMolar (μM) range. Docking experiments were carried out in order to compare the theoretical and experimental affinity of these compounds to the hMAO-B protein. According to our results, docking experiments could be an interesting approach to try to predict the activity of this class of coumarins against MAO-B receptors.

Tyrosinase inhibitor activity of coumarin-resveratrol hybrids.

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl)-6,8-dihydroxycoumarin (8) is the most potent compound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

MAO Inhibitory Activity of 2-Arylbenzofurans versus 3-Arylcoumarins: Synthesis, in vitro Study, and Docking Calculations

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Several 3‐arylcoumarin derivatives were previously described as interesting selective MAO‐B inhibitors. Preserving the trans‐stilbene structure, a series of 2‐arylbenzofuran and corresponding 3‐arylcoumarin derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO‐A and MAO‐B. In general, both types of derivatives were found to be selective MAO‐B inhibitors, with IC50 values in the nano‐ to micromolar range. 5‐Nitro‐2‐(4‐methoxyphenyl)benzofuran (8) is the most active compound of the benzofuran series, presenting MAO‐B selectivity and reversible inhibition (IC50=140 nM). 3‐(4′‐Methoxyphenyl)‐6‐nitrocoumarin (15), with the same substitution pattern as that of compound 8, was found to be the most active MAO‐B inhibitor of the coumarin series (IC50=3 nM). However, 3‐phenylcoumarin 14 showed activity in the same range (IC50=6 nM), is reversible, and also severalfold more selective than compound 15. Docking experiments for the most active compounds into the MAO‐B and MAO‐A binding pockets highlighted different interactions between the derivative classes (2‐arylbenzofurans and 3‐arylcoumarins), and provided new information about the enzyme–inhibitor interaction and the potential therapeutic application of these scaffolds.

Synthesis and complete assignment of the 1H and 13C NMR signals of some oxopyrancoumarin and oxofuropyrancoumarin derivatives

The synthesis of four pyranocoumarins starting from phloroglucinol and the complete 1H and 13C NMR assignment of seven pyranocoumarins has been performed using 1D and 2D NMR techniques including COSY, HMQC and HMBC experiments. Copyright