10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I

T Gallardo; J Saez; H Granados; J R Tormo; I D Velez; N Brun; B Torres; D Cortes

doi:10.1021/np980079+

10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I

J Nat Prod. 1998 Aug;61(8):1001-5. doi: 10.1021/np980079+.

Authors

T Gallardo¹, J Saez, H Granados, J R Tormo, I D Velez, N Brun, B Torres, D Cortes

Affiliation

¹ Departamento de Farmacología, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.

PMID: 9722484
DOI: 10.1021/np980079+

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimetabolites, Antineoplastic / isolation & purification*
Antimetabolites, Antineoplastic / pharmacology
Antineoplastic Agents, Phytogenic / isolation & purification*
Antineoplastic Agents, Phytogenic / pharmacology
Cattle
Electron Transport / drug effects*
Furans / isolation & purification*
Furans / pharmacology
In Vitro Techniques
Lactones / isolation & purification*
Lactones / pharmacology
Magnetic Resonance Spectroscopy
Mass Spectrometry
Mitochondria, Heart / drug effects
Mitochondria, Heart / metabolism*
Plants, Medicinal / chemistry*
Seeds / chemistry
Spectrophotometry, Infrared
Spectrophotometry, Ultraviolet

Substances

10-oximeguanacone
Antimetabolites, Antineoplastic
Antineoplastic Agents, Phytogenic
Furans
Lactones