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

ABSTRACT: Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1H)-pyridinone have been designed and synthesised.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.

SUBMITTER: Bergin JCJ 

PROVIDER: S-EPMC9101691 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Bergin Joseph C J JCJ   Tan Kean Kan KK   Nelson Anya K AK   Amarandei Cristina-Andreea CA   Hubscher-Bruder Véronique V   Brandel Jérémy J   Voinarovska Varvara V   Dejaegere Annick A   Stote Roland H RH   Tétard David D  

Molecules (Basel, Switzerland) 20220428 9

Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1<i>H</i>)-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 <i>O</i>-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 as  ...[more]

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