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

doi:10.1248/cpb.56.1738

Notes

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

Author information

Kouji Kuramochi
Department of Applied Biological Science, Tokyo University of Science
Genome and Drug Discovery Center, Tokyo University of Science
Kensuke Ohnishi
Genome and Drug Discovery Center, Tokyo University of Science
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Satoshi Fujieda
Department of Applied Biological Science, Tokyo University of Science
Mitsuhiro Nakajima
Department of Applied Biological Science, Tokyo University of Science
Yoshihiko Saitoh
Department of Applied Biological Science, Tokyo University of Science
Nobuo Watanabe
Department of Applied Biological Science, Tokyo University of Science
Toshifumi Takeuchi
Department of Applied Biological Science, Tokyo University of Science
Atsuo Nakazaki
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Fumio Sugawara
Department of Applied Biological Science, Tokyo University of Science
Genome and Drug Discovery Center, Tokyo University of Science
Takao Arai
Department of Applied Biological Science, Tokyo University of Science
Susumu Kobayashi
Genome and Drug Discovery Center, Tokyo University of Science
Faculty of Pharmaceutical Sciences, Tokyo University of Science

Keywords: neoechinulin A, structure–activity relationship, reactive oxygen species, reactive nitrogen species, antioxidant

JOURNAL FREE ACCESS

2008 Volume 56 Issue 12 Pages 1738-1743

DOI https://doi.org/10.1248/cpb.56.1738

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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.

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