Development of a Mitochondriotropic Antioxidant Based on Caffeic Acid: Proof of Concept on Cellular and Mitochondrial Oxidative Stress Models

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Teixeira, J (Author) Other; Fernando Cagide (Author) FCUP; Benfeito, S (Author) Other; Soares, P (Author) Other; Garrido, J (Author) Other; Baldeiras, I (Author) Other; José A. Ribeiro (Author) FCUP; Carlos M Pereira (Author) FCUP; Silva, F (Author) FCUP; Paula B Andrade (Author) FFUP; Oliveira, PJ (Author) Other; Fernanda Borges (Author) FCUP

Journal

Title: Journal of Medicinal Chemistry

Vol. 60

Pages: 7084-7098

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 50 Citations

Scopus - 51 Citations

Other information

Authenticus ID: P-00M-XZ6

DOI: 10.1021/acs.jmedchem.7b00741

Abstract (EN): Targeting mitochondrial oxidative stress is an effective therapeutic strategy. In this context, a rational design of mitochondriotropic antioxidants (compounds 22-27) based on a dietary antioxidant (caffeic acid) was performed. Jointly named as AntiOxCINs, these molecules take advantage of the known ability of the triphenylphosphonium cation to target active molecules to mitochondria. The study was guided by structure-activity-toxicity-property relationships, and we demonstrate in this work that the novel AntiOxCINs act as mitochondriotropic antioxidants. In general, AntiOxCINs derivatives prevented lipid peroxidation and acted as inhibitors of the mitochondrial permeability transition pore. AntiOxCINs toxicity profile was found to be dependent on the structural modifications performed on the dietary antioxidant. On the basis of mitochondrial and cytotoxicity/antioxidant cellular data, compound 25 emerged as a potential candidate for the development of a drug candidate with therapeutic application in mitochondrial oxidative stress-related diseases. Compound 25 increased GSH intracellular levels and showed no toxicity on mitochondrial morphology and function.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15