Indoles antioxidants

Some non-enzymatic antioxidants play a key role in these defense mechanisms. These are often vitamins (A, C, E, K), minerals (zinc, selenium), caretenoids, organosulfur compounds, allyl sulfide, indoles, antioxidant cofactors (coenzyme Qio)> and polyphenols (flavonoids and phenolic acids) [1,37]. Further, there is good evidence that bilirubin and uric acid can act as antioxidants to help neutralize certain free radicals [38]. Alpha-carotene, lycopene, lutein, and zeaxanthine [39] can be considered subgroups of carotenoids [40] that are effective antioxidant compounds. 

Antioxidant Activities of Synthetic Indole Derivatives and Possible Activity Mechanisms... 

Shertzer HG, Sainsbury M. 1991. Chemoprotective and hepatic enzyme induction properties of indole and indenoindole antioxidants in rats. Food Chem Toxicol 29 391-400. 

Synthetic Indole Derivatives having in Vitro Antioxidant Activity. 151... 

Indole Derivatives Connected to a Known Antioxidant Molecule. 156... 

Keywords Indole Melatonin Antioxidant activity Oxidative stress Mechanism... 

According to Tan et al. [45], the methoxy group in the 5th position of the indole ring keeps melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, the antioxidant capacity of this molecule may be enhanced. The changes could be decreased lipophility and increased prooxidative activity. 

SAR studies on melatonin analogues showed that methoxy and amido moieties are important for binding to melatonin receptors various substituents on the 2nd position of the indole ring enhance the binding affinity [52-54]. The conformational flexibility of the C-3 ethylamido side chain is probably responsible for the broad spectrum of biological activities. As a powerful antioxidant melatonin was shown to have significantly broader actions including oncostatic effects [55], immune system stimulation [56], and antiinflammatory functions [57,58]. 

The indolic nitrogen is the active redox center of indoles, due to its lone pair of electrons [101,102]. Indeed, if the oxygen replaces the nitrogen in the indolic ring, the antioxidant activity of the resulting benzofurane is much lower [47]. Delocalization of this electron pair over the aromatic system seems to be of great importance for antioxidant activity of indole derivatives. 

Evaluation of the scavenging activity for H2O2 by NSAIDs, namely indole derivatives (indomethacin, acemetacin, etodolac), pyrrole derivatives (tol-metin, ketorolac), oxazole derivative (oxaprozin), indene derivative (sulin-dac) and its metabolites (sulindac sulfide and sulindac sulfone) was performed by Costa et al. [ 103]. The obtained results against endogenous antioxidants melatonin and GSH demonstrated that all the studied NSAIDs display... 

Stobadine ((-)-cis-2,8 dimethyl-2,3,4,4a,5,9b-hexahydro-l-H-pyrido (4,3b) indole) is a model drug with pyridoindole structure with cardioprotective and antioxidant properties [109]. Based on stobadine, (-)-ris-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-lH-pyrido[4,3-b]indole (Fig. 4), a well-known antioxidant, free-radical scavenger and neuroprotectant, stobadine derivatives with improved pharmacodynamic and toxicity profiles were developed [110]. A stobadine molecule was modified mostly by electron donating substitution on the benzene ring and by alkoxycarbonyl substitution at N-2 position. Significant antioxidant activity was observed in the new compounds. A link... 

The synthesis [111] and examination of 1-p-toluenesulfonyl-6,7,8,9-lelrahydro-N,N-di- -propyl-lH-bcnz [g]indol-7-amine (TPBIA in Fig. 5) for behavioral effects in rats related to interactions with central dopamine receptors showed remarkable antioxidant activity. Because TPBIA has increased lipophilicity, penetrating the blood-brain barrier in a considerable degree was expected and it was found that it completely inhibits the peroxidation of rat liver microsome preparations [112]. 

Oxidative stress appears to have a central role in the induction of apoptosis following the exposure of cells to a range of cytotoxic insults. Anti-apoptotic properties of the antioxidant, 4b,5,9b,10-tetrahydroindeno[l,2-b]indole, in Jurkat T cells subjected to a number of cytotoxic insults. Peroxide and superoxide anion production following UV treatment showed that indole derivative was found to only partially inhibit superoxide anion production and exhibited strong inhibition of caspase-3 activation in UV [115]. 

Antioxidants of a different chemical nature have been investigated for use as therapeutic agents, either alone or in combination. Combination of a known antioxidant compound with indole ring or melatonin analogue compounds is a new trend in antioxidant chemistry. 

Also, antioxidant properties of conjugates based on indole and lipoic acid moieties (Fig. 8) were studied. The target compounds showed reasonable antioxidant properties using rat liver microsomal, NADPH-dependent LP in-... 

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