Extraction And Structural Modification Of Antitumor Constituents From Veratrum Dahuricum

Veratrum dahuricum (Liliaceae) is one of the 14 species of the genus Veratrum in China. The rhizomes of some Veratrum species incuding Veratrum dahuricum, named as Lilu in Chinese traditional medicine, are used for some diseases such as aphasia arising apoplexy, epilepsy, wind type dysentery, jaundice, chronic malaria and acariasis. The crude extracts and compounds isolated from Veratrum plant havd been reported possessing various pharmacological activities, including hypotensive, antithrombotic and antitumor function.1. Chemical investigation of Veratrum dahuricumBy modern chromatographic methods,10 compounds were isolated from the ethanol extract of rhizomes of Veratrum dahuricum. Their structures were elucidated on the basis of spectral data including 1H-NMR,13C-NMR, DEPT,1H-1HCOSY, NOESY, HMQC, HMBC, ESI-MS, IR, as follows:XL-1: XL-4: Jervine14α-hydroxy-Δ11-cyclopamine XL-5:VeratramineXL-2:Veratrobasine XL-6:VeratrsineXL-3:Cyclopamine XL-7:Pseudojervine XL-8:Verazine XL-10:ResveratrolXL-9:Germine2. Pharmacology research on Veratrum dahuricumThe acute toxic trials showed that the total alkaloids extract was the most toxic of all the samples, including petroleum ether, CHCl3, EtOAC, n-BuOH fraction, ethanol extract and total alkaloids. The better cytotoxic and antitumor activities were found on the jerveratrum alkaloids compared to the ceveratrum alkaloids.3. The modification of three active compoundsWe have gained above 10 derivatives of veratramine, jervine by chemical and biotransformational methods. Among them,3 compounds further optimized exhibited significent activities. Especially, cyclopamine from Veratrum plant we studied, a special inhibitor to the Hedgehog signal pathway, had significant antitumor avtivity.