Comparison of free-radical inhibiting antioxidant properties of carvedilol and its phenolic metabolites

Abstract

Carvedilol is a widely prescribed drug for the treatment of heart failure and the prevention of associated ventricular arrhythmias. It has also been reported to function as a biological antioxidant hydrogen atom transfer from its carbazole N-H moiety to chain-propagating radicals. Metabolites of the drug include phenolic derivatives, such as 3-hydroxy-, 4'-hydroxy- and 5'-hydroxycarvedilol, which are also potential antioxidants. A comparison of the radical-inhibiting activities of the parent drug and the three metabolites was carried out in two separate assays. In the first, hydrogen atom transfer from these four compounds to the stable radical DPPH was measured by the decrease in the UV-visible absorption at 515 nm of the latter. The known radical inhibitors BHT, 4-hydroxycarbazole and α-tocopherol were employed as benchmarks in parallel experiments. In the second assay, inhibition of the photoinduced free-radical 1,2-addition of-phenyl -tolueneselenosulfonate to cyclopropylacetylene, along with competing ring-opening of the cyclopropane ring, was monitored byH NMR spectroscopy in the presence of the carvedilol-based and benchmark antioxidants. In both assays, carvedilol displayed negligible antioxidant activity, while the three metabolites all proved superior radical inhibitors to BHT, with radical-quenching abilities in the order 3-hydroxy- > 5'-hydroxy > 4'-hydroxycarvedilol. Among the metabolites, 3-hydroxycarvedilol displayed even stronger activity in both assays than α-tocopherol, the best of the benchmark antioxidants. These results suggest that the radical-inhibiting antioxidant properties that have been attributed to carvedilol are largely or exclusively due to its metabolites and not to the parent drug itself.

The β-Blocker Carvedilol Prevented Ultraviolet-Mediated Damage of Murine Epidermal Cells and 3D Human Reconstructed Skin

“…Metoprolol was used as a control β-blocker without anti-transformation activity [9] and without proven antioxidant property [19], but is a commonly used β-blocker. 4-OHC is an intermediate compound in carvedilol synthesis that acted as a free radical scavenger (i.e., chemical antioxidant) [20]. Carvedilol-mediated protective effects were unique as neither UV-nor H 2 O 2 -mediated reductions in cell viability were altered by metoprolol or 4-OHC.…”

“…The present study first examined whether carvedilol could protect murine epidermal cells against UV or hydrogen peroxide (H 2 O 2 )-induced oxidative damage, a known precursor event leading to skin carcinogenesis [18]. Carvedilol's protective activity was compared with metoprolol, a β-blocker without proven antioxidant property [19], and an intermediate compound for carvedilol synthesis, 4-hydroxycarbazole (4-OHC), which possesses a chemical antioxidant activity [20]. In previous studies, metoprolol and 4-OHC did not show cancer preventive efficacy when compared with carvedilol in vitro and in vivo [7,9].…”

Benchmarking Antioxidant-Related Properties for Gallic Acid through the Use of DFT, MP2, CCSD, and CCSD(T) Approaches

“…according to differences in their chemical structures. Due to the fact that these entities are highly desired for providing several health-related features (such as anti-inflammatory, antiviral, and antitumor actions − ), there is an ongoing focus in chemical, food, and pharmaceutical industries on finding sources of antioxidants.…”

Kinetics and Mechanism of the Antioxidant Activities of C. olitorius and V. amygdalina by Spectrophotometric and DFT Methods

“…Many investigations − have been carried out to understand the kinetics and mechanisms of radical scavenging activities of phenolic antioxidants. According to the literature, the kinetics of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activities of phenolic antioxidants in the extracts of different plant species has been compared.…”