Cellular and Mitochondrial Toxicity of Tolcapone, Entacapone, and New Nitrocatechol Derivatives.

ABSTRACT: Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O-methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver. There is a knowledge gap concerning which mechanisms and chemical properties govern the toxicity of nitrocatechol-based COMT inhibitors. Using a vast array of cell-based assays, we found that tolcapone-induced toxicity is caused by direct interference with mitochondria that

SUBMITTER: Pinto M 

PROVIDER: S-EPMC11091965 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature