neoechinulin-a and 3-nitrotyrosine

We synthesized a series of neoechinulin A derivatives and examined the structure-activity relationships in terms of their anti-nitration and anti-oxidant activities as well as their cytoprotective activity against peroxynitrite from SIN-1 (3-(4-morpholinyl)sydnonimine hydrochloride) using PC12 cells. Our results showed that the C-8/C-9 double bond, which constitutes a conjugate system with indole and diketopiperazine moieties of neoechinulin A is essential for anti-nitration and anti-oxidant activities as well as protection against SIN-1 cytotoxicity. The presence of an intact diketopiperazine moiety is an additional requirement for anti-nitration activity but not for the cytoprotective action. Our results suggest that the antioxidant activity or electrophilic nature of the C-8 carbon, both of which are afforded by the C-8/C-9 double bond, may play a role in the cytoprotective properties of this alkaloid.

Topics: Animals; Antioxidants; Brain Chemistry; Cell Survival; Indicators and Reagents; Indole Alkaloids; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Molsidomine; Nitrates; PC12 Cells; Peroxynitrous Acid; Piperazines; Protective Agents; Rats; Structure-Activity Relationship; Tyrosine