10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I.
A new 10-keto bis-tetrahydrofuran acetogenin, guanacone (1), has been isolated from a cytotoxic extract of Annona aff. spraguei seeds. The 10-oximeguanacone derivative 1f is the first bioactive nitrogenated acetogenin found to be a very potent inhibitor of complex I. In addition, a SAR study of guanacone analogues is reported based on the titration of the NADH oxidase and NADH:ubiquinone oxidoreductase activities.
Departamento de Farmacología, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
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T
Gallardo
J
J
Saez
H
H
Granados
J R
JR
Tormo
I D
ID
Velez
N
N
Brun
B
B
Torres
D
D
Cortes
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects*; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010946:Plants, Medicinal / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
C114802:10-oximeguanacone; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007783:Lactones