17 research outputs found
Antioxidant potential of natural and synthesised polyprenylated hydroquinones
The metabolites 2-octaprenyl-1,4-hydroquinone (1) and
2-(24-hydroxy)-octaprenyl-1,4-hydroquinone (2), isolated from the sponge
Ircinia spinosula. along with a series of synthetic derivatives, were
evaluated for their antioxidant capacity, in order to establish a
potential relationship between structural characteristics and
antioxidant activity. The antioxidant potential of both natural and
synthesised compounds was evaluated in vitro by their ability: (1) to
interact with the stable free 1,1-diphenyl-2-picrylhydrazyl radical
(DPPH) and (2) to inhibit the peroxidation, induced by the
Fe++/ascorbate system, of heat inactivated hepatic microsomal membrane
lipids. Metabolite 1 presented a strong interaction with DPPH and had a
moderate effect on lipid peroxidation. while metabolite 2 interacted
extensively with DPPH and exhibited a significant effect against lipid
peroxidation. All derivatives retaining the free 1,4-hydroquinone system
maintained fully or partly the free radical scavenging capacity. (C)
2002 Elsevier Science Ltd. All rights reserved
Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Potential Therapeutic Approach against Atherosclerosis
In line with our previous studies, we have developed through a rational design approach novel morpholine and benzoxa(or thia)zine lead compounds that modulate a multiplicity of targets against atherosclerosis. We have evaluated the most promising compounds for their efficiency to a) interact and scavenge free radicals, b) inhibit the metal ion (Cu2+)-induced LDL oxidation c) act intracellularly as antioxidants in THP- 1 monocytes from a leukemic patient and d) inhibit the pro-inflammatory enzymes cycloxygenase-1 (COX-1) and -2 (COX-2) in vitro. Furthermore, two representative compounds were tested for their potential to decrease lipidemic parameters (TC, LDL and TG) in hyperlipidemic mice. Most derivatives indicated a remarkable antioxidant activity, while at the same time exhibited a significant in vitro anti-inflammatory activity, inhibiting COX-1 or/and COX-2 activity at 20 μΜ. Furthermore, after their long-term administration, compounds 6 and 8 afforded a considerable activity in a chronic experimental animal model of hyperlipidemia (after high fat diet administration). The multifunctional pharmacological profile exhibited by the compounds of this study renders them interesting lead compounds for the development of novel agents against atherosclerosis