Studies On Chemical Constituents And Anti-pancreatic Cancer Activity Of Ferula Sinkiangensis

Ferula is a generic name for the plants of the genus Ferula in the Umbrellaceae,which mainly occur in deserts and clayey slopes with gravel at an altitude of 850 m.There are about 180 species of the genus Ferula,which are mainly distributed in the Mediterranean region of southern Europe and northern Africa.Among them,there are twenty-five species in China,mainly produced in Xinjiang region.Ferula has high medicinal value.Modern pharmacological research has found that its components have the effects of anticancer,insect repellent,anti epileptic,antioxidant,antibacterial,antihypertensive,anticoagulant,labor pain,and hypnotic.Currently,it has been found that the main components in Ferula include sulfur compounds,sesquiterpenes,phenylpropanoid,and dimers of sesquiterpenes.In this study,thirty-three compounds were isolated from the ethyl acetate fraction of the root of Ferula sinkiangensis,and seventeen of them were new structures,including three sesquiterpenoid chromogens,eight coumarin sesquiterpenoid dimers,one phenylpropyl sesquiterpene dimer derivative and five sesquiterpenoids.Some of its compounds were tested for their anti pancreatic cancer activity.The specific research results are as follows:First,the five new sesquiterpenoid compounds isolated all contain the same sesquiterpenoid units,including a furan ring and a peroxy six ring.In this category,these new sesquiterpenoid structures have been analyzed in detail.Three new sesquiterpene chromones were isolated,including one new carbon skeleton and two new oxygen-containing frameworks.The new carbon skeleton is named ferulasin A.Its structure is that the side chain sesquiterpenes C-1’and C-5’form a cyclopentane,and C-7’form an oxygen-containing 7-membered ring with chromone C-2.Two unreported sesquiterpene chromones,（±）-ferulasin,were isolated from the roots of Ferula sinkiangensis.Ferulasin shows one uncommon oxygen-containing macrocyclic structure with one trioxaspiro,and represents a new framework in which the side chain sesquiterpene C-10’and C-11’form an oxygen-containing13-membered ring with chromone C-2.The chemical structure was established by diverse spectroscopic methods,X-ray crystallographic analyses and ECD calculations.（±）-Ferulasin exhibited potent cytotoxicity against pancreatic cancer cells with IC₅₀values ranging from 0.92±0.12 to 19.13±2.99μM.Eight new sesquiterpene coumarins were isolated,of which six were 2-pentenylpyridine sesquiterpene coumarin and two were ring-opening sesquiterpene coumarin.Two pairs of 2-pentenylpyridine sesquiterpene coumarin dimers were successfully separated.The anti pancreatic cancer activity of eight new structures was tested.Next,Sixteen known compounds were isolated and identified,including three sesquiterpenes,three sesquiterpene coumarin dimers,seven sesquiterpene phenylpropanoid derivativesand and three simple compounds.Among the known compounds,eleven compounds were reported from F.Sinkiangensis for the first time.Herein,we discussed the chemotaxonomic significance of the isolated compounds.Moreover,compounds 18、15、11、12、13、20、19 were shown to significantly inhibit cell viability respectively in Capan-2 cell lines,with a decline of the cell survival of66.95%,24.22%,98.47%,36.32%,68.92%,29.49%,59.40%（p<0.05）.They are potential drugs for anti-pancreatic cancer treatment.All chemical structures here are determined by literature comparison,different spectral methods,X-ray single crystal diffraction analysis and ECD calculation.In this paper,the chemical structures and biological activities of Ferula were classified.And seventeen new structures were isolated from the roots of F.Sinkiangensis,which expanded the natural product database.Strong activity were found,laying a foundation for better utilization of plant resources with Chinese characteristics.