Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Teixeira, J (Author) Other; Oliveira, C (Author) Other; Fernando Cagide (Author) FCUP; Amorim, R (Author) Other; Garrido, J (Author) Other; Fernanda Borges (Author) FCUP; Oliveira, PJ (Author) Other

Journal

Title: Journal of Enzyme Inhibition and Medicinal Chemistry

Vol. 33

Pages: 567-576

ISSN: 1475-6366

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 19 Citations

Other information

Authenticus ID: P-00N-RAX

DOI: 10.1080/14756366.2018.1442831

Abstract (EN): Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN(3)) based on the dietary antioxidant gallic acid was developed. AntiOxBEN(3) accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN(3) showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN(3) presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN(3) strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN(3) can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders. [GRAPHICS] .

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10