: Cyclopamine (1), the teratogenic steroidal alkaloid isolated from corn lily (Veratrum californicum), has recently gained renewed interest due to its anticancer potential, that has been translated into the FDA approval of three Hedgehog (Hh) pathway inhibiting antitumor drugs. A chemical analysis of mother liquors obtained from crystallization of cyclopamine, extracted from roots and rhizomes of V. californicum, resulted in the isolation of two unprecedented cyclopamine analogues, 18-hydroxycyclopamine (2) and 24R-hydroxycyclopamine (3), the first compounds of this class to show modifications on rings D-F. The stereostructures of these new natural compounds have been established based on a detailed MS and 1D/2D NMR investigation. The isolated compounds were evaluated with the dual-luciferase bioassay for their inhibition of the hedgehog pathway in comparison to cyclopamine, providing new insights into the structure-activity relationships for this class of compounds.
Hydroxylated cyclopamine analogues from Veratrum californicum and their hedgehog pathway inhibiting activity / Chianese, Giuseppina; Lopatriello, Annalisa; Sirignano, Carmina; Andreani, Alessandro; Gambini, Andrea; De Combarieu, Eric; Stornaiuolo, Mariano; Taglialatela-Scafati, Orazio. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 84:(2023), p. 117265. [10.1016/j.bmc.2023.117265]
Hydroxylated cyclopamine analogues from Veratrum californicum and their hedgehog pathway inhibiting activity
Chianese, GiuseppinaPrimo
Investigation
;Lopatriello, AnnalisaSecondo
Membro del Collaboration Group
;Sirignano, CarminaInvestigation
;Stornaiuolo, MarianoPenultimo
Investigation
;Taglialatela-Scafati, Orazio
Ultimo
Conceptualization
2023
Abstract
: Cyclopamine (1), the teratogenic steroidal alkaloid isolated from corn lily (Veratrum californicum), has recently gained renewed interest due to its anticancer potential, that has been translated into the FDA approval of three Hedgehog (Hh) pathway inhibiting antitumor drugs. A chemical analysis of mother liquors obtained from crystallization of cyclopamine, extracted from roots and rhizomes of V. californicum, resulted in the isolation of two unprecedented cyclopamine analogues, 18-hydroxycyclopamine (2) and 24R-hydroxycyclopamine (3), the first compounds of this class to show modifications on rings D-F. The stereostructures of these new natural compounds have been established based on a detailed MS and 1D/2D NMR investigation. The isolated compounds were evaluated with the dual-luciferase bioassay for their inhibition of the hedgehog pathway in comparison to cyclopamine, providing new insights into the structure-activity relationships for this class of compounds.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.