Inactivation of the cytotoxic activity of repin, a sesquiterpene lactone from Centaurea repens

Chemical Research in Toxicology
Francis F TukovJohn M Rimoldi

Abstract

Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell line have led to the identification of one of several putative agents, which may contribute to ENE, namely, the sesquiterpene lactone (SQL) repin (1), previously linked to ENE due to its abundance in C. repens. To characterize the molecular basis of repin-induced neurotoxicity, the present study was designed to identify reactive functional groups that may contribute overall to its toxicity. The reaction of repin (1) with glutathione (GSH) led to the exclusive addition of GSH to the alpha-methylenebutyrolactone affording a GSH conjugate (3b) that lacked toxicity in the PC12 cell assay, while selective reduction of the alpha-methylenebutyrolactone double bond of 1 also resulted in an analogue (2) that was devoid of toxicity relative to the parent compound. Unlike repin, analogue 2 failed to decrease cellular dopamine levels in PC12 cells, further substantiating the requirement of the alpha-methylenebutyrolactone group....Continue Reading

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Citations

Mar 27, 2012·Australian Veterinary Journal·C R B Elliott, C I McCowan
Jul 24, 2013·Critical Reviews in Toxicology·M Helena R AmorimMargarida M S M Bastos
Jun 4, 2015·The Veterinary Clinics of North America. Equine Practice·Ahmad Al-Dissi
Apr 26, 2013·Journal of Natural Products·Horacio A Priestap, Manuel A Barbieri
Dec 18, 2007·Chemistry & Biodiversity·Danilo D RochaLetícia V Costa-Lotufo
Dec 30, 2020·International Journal of Molecular Sciences·Francisco Estévez-SarmientoFrancisco Estévez
May 15, 2007·Mutation Research·Marne C VasconcellosJoão Antônio Pegas Henriques

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