8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity

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

Authors

Carrageta, DF (Author) Other; Dias, TR (Author) Other; Jarak, I (Author) Other; Alves, MG (Author) Other; Oliveira, PF (Author) FMUP; Van der Walt, MM (Author) Other; Terre'Blanchee, G (Author) Other; Monteiro, M (Author) ICBAS; Silva, BM (Author) Other

Journal

Title: Toxicology in Vitro

Vol. 53

Pages: 114-120

ISSN: 0887-2333

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00P-GSB

DOI: 10.1016/j.tiv.2018.08.002

Abstract (EN): Caffeine is one of the most worldwide consumed methylxanthines. It is well-known for its thermogenic and cell metabolism modulating effects. Based on methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine (PTX) is a novel adenosine antagonist with higher receptor affinity than caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger than those of caffeine. For that purpose, murine 3T3-L1 cells were cultured in the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 mu M) for 24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and lactate dehydrogenase (LDH) release. Cell metabolites released to the culture medium were identified and quantified by proton nuclear magnetic resonance (H-1 NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX displayed no signs of cytotoxicity at all studied concentrations. When compared with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as well as lactate, alanine, and acetate production. Additionally, PTX decreased protein oxidation, thus protecting against oxidative stress-induced damage. These results illustrate that PTX is a stronger and less cytotoxic caffeine substitute with potential applications as metabolic modulator and a good candidate for novel drug design.

Language: English

Type (Professor's evaluation): Dissemination

No. of pages: 7