Synthesis and biological activities of neoechinulin A derivatives: New aspects of structure-activity relationships for neoechinulin A

Kouji Kuramochi, Kensuke Ohnishi, Satoshi Fujieda, Mitsuhiro Nakajima, Yoshihiko Saitoh, Nobuo Watanabe, Toshifumi Takeuchi, Atsuo Nakazaki, Fumio Sugawara, Takao Arai, Susumu Kobayashi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1738-1743
Number of pages6
JournalChemical and Pharmaceutical Bulletin
Volume56
Issue number12
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Antioxidant
  • Neoechinulin A
  • Reactive nitrogen species
  • Reactive oxygen species
  • Structure-activity relationship

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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