Abstract
Neoechinulin A, an alkaloid from Eurotium rubrum Hiji025, protected neuronal PC12 cells against cell death induced by peroxynitrite derived from SIN-1 (3-(4-morpholinyl)sydnonimine hydrochloride). In this study, we investigated the structure-activity relationships of neoechinulin A and a set of its analogues by using assays to measure anti-nitration and antioxidant activities and cytoprotection against SIN-1-induced PC12 cell death. The presence of the diketopiperazine ring was essential for both the antioxidant and anti-nitration activities of neoechinulin A derivatives. Nevertheless, a derivative lacking the diketopiperazine ring could still protect PC12 cells against SIN-1 cytotoxicity. An acyclic analogue completely lost the cytoprotective effect while retaining its antioxidant/antinitration activities. Pre-incubation of the cells with neoechinulin A for at least 12 hours was essential for the cells to gain SIN-1 resistance. These results suggest that neoechinulin A endows the cells with cytoprotection through a biological effect different from the apparent antioxidant/anti-nitration activities.
Original language | English |
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Pages (from-to) | 614-621 |
Number of pages | 8 |
Journal | Journal of Antibiotics |
Volume | 60 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2007 Oct |
Externally published | Yes |
Keywords
- Alkaloid
- Neoechinulin
- Reactive oxygen/nitrogen species
- Structure-activity relationship
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery