1-Hydroxy-2(1H)-pyridinone-Based Chelators with Potential Catechol O-Methyl Transferase Inhibition and Neurorescue Dual Action against Parkinson's Disease

被引：1

作者：

Bergin, Joseph C. J. ^{[1
]}

Tan, Kean Kan ^{[1
]}

Nelson, Anya K. ^{[1
]}

Amarandei, Cristina-Andreea ^{[2
]}

Hubscher-Bruder, Veronique ^{[2
]}

Brandel, Jeremy ^{[2
]}

Voinarovska, Varvara ^{[3
]}

Dejaegere, Annick ^{[3
]}

Stote, Roland H. ^{[3
]}

Tetard, David ^{[1
]}

机构：

[1] Northumbria Univ, Fac Hlth & Life Sci, Dept Appl Sci, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England

[2] Univ Strasbourg, CNRS, IPHC, UMR 7178, F-67000 Strasbourg, France

[3] Univ Strasbourg, Ctr Natl Rech Sci CNRS, Inst Natl Sante & Rech Med INSERM, Inst Genet & Biol Mol & Cellulaire IGBMC,UMR7104, F-67404 Illkirch Graffenstaden, France

来源：

MOLECULES | 2022年 / 27卷 / 09期

关键词：

1-hydroxy-2(1H)-pyridinone; catechol O-methyl transferase; Parkinson's disease; METHYLTRANSFERASE COMT INHIBITORS; MEDICINAL CHEMISTRY; MOLECULES; TOLCAPONE; PHARMACOKINETICS; SEQUESTRATION; ENTACAPONE; COMPLEX; CHARMM; MODEL;

D O I：

10.3390/molecules27092816

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1H)-pyridinone have been designed and synthesised. These compounds are expected to have a dual mode of action both beneficial against Parkinson's disease: they are designed to be inhibitors of catechol O-methyl transferase, which contribute to the reduction of dopamine in the brain, and to protect neurons against oxidative damage. To assess whether these compounds are worthy of biological assessment to demonstrate these effects, measurement of their pKa and stability constants for Fe(III), in silico modelling of their potential to inhibit COMT and blood-brain barrier scoring were performed. These results demonstrate that the compounds may indeed have the desired properties, indicating they are indeed promising candidates for further evaluation.

引用

页数：19

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