title: Synthesis and biological activities of neoechinulin A derivatives: new aspects of structure-activity relationships for neoechinulin A.
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.
authors.affiliation: Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kuramochi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujieda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Nobuo
authors.initials: N
authors.lastname: Watanabe
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Takao
authors.initials: T
authors.lastname: Arai
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry*; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008981:Molsidomine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D009566:Nitrates / Q000737:chemistry; D016716:PC12 Cells; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D020011:Protective Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000975:Antioxidants; D007202:Indicators and Reagents; D026121:Indole Alkaloids; D009566:Nitrates; D010879:Piperazines; D020011:Protective Agents; C490266:neoechinulin A; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine