Comparative Evaluation of Biochemical Antioxidants as Neuroprotective Agents

Is the chromanol head group of vitamin E nature's final truth on chain-breaking antioxidants?

AbstractTocopherol is believed to be the most potent naturally occurring chain-breaking antioxidant. Hence, its refined phenolic head group chromanol may represent an optimum evolutionary solution to the problem of free-radical chain reactions in the lipid bilayer. To test the universal validity of this assumption beyond phenolic head groups, we have synthesized aromatic amine analogues of vitamin E and trolox with otherwise closely matching physicochemical properties: NH-toc and NH-trox. We have found that NH-toc and NH-trox were significantly more potent free radical scavengers, lipid peroxidation inhibitors and cytoprotective agents than their phenolic templates, tocopherol and trolox. I…

Phenothiazine: the seven lives of pharmacology's first lead structure.

Rooted in the early days of organic dye chemistry, the phenothiazine structure and its derivatives have since held a prominent place in pharmacology and biomedicine. Initially used for histochemical stains of plasmodia by Paul Ehrlich, anthelmintic and antibiotic properties of phenothiazines were globally exploited in the 1930s and 1940s. Clinical use of N-substituted phenothiazines as antihistaminics (1940s), sedatives and antipsychotics (1950s) followed and continues to this day. Recently, interest in these structures has re-emerged for a variety of fascinating features in relation to neurodegenerative disease, spearheaded by the unique redox chemistry of phenothiazine--arguably the most …