Sesquiterpenes From Carpesium Abrotanoides L And Their Cytotoxic Activity

Carpesium abrotanoides L.（Compositae）is an ethnomedicine especially in the area of Tujia nationality.The seeds of Carpesium abrotanoides L has a long history of medicinal use for treating various diseases such as ascariasis,enterobiasis,cestodiasis and abdominal pain due to parasitic infestation.The whole plant of Carpesium abrotanoides L has been used for treating sore throats,tonsillitis,bronchitis,etc.Modern pharmacological researches shows that Carpesium abrotanoides L has various biological activities such as antitumor,antiviral and antibacterial avtivities.However,the research on the chemical constituents from Carpesium abrotanoides L and their pharmacological mechanisms are still insufficient.Therefore,the study of chemical constituents from Carpesium abrotanoides L and their cytotoxic activity will be important for the knowledge of its substance basis of activity.More over,as a famous folk medicine in Tujia nationality,Carpesium abrotanoides L has been admitted to"Annals of Chinese ethnodrug"and"Quality Standard of Chinese medicinal materials in Hubei Province".This paper also provides scientific basis not only for the establishment of quality standards,but also for the rational use and further research and development of Carpesium abrotanoides L.The air-dried whole plant of Carpesium abrotanoides L was extracted with 95%ethanol in room temperature.After the removal of solvent in vacuo,the ethanol extract was extracted with petroleum ether,ethyl acetate and n-BuOH,respectively.The cytotoxic activities of these 4 extracts against 8 different human cancer cell lines were evaluated by MTT assay.We choose the ethyl acetate extract for further phytochemistry investigation based on the the bioassay result.Compounds were isolated by positive and reverse phase silica gel column chromatography,vacuum liquid chromatography and preparative high performance liquid chromatography（Pre-HPLC）.The planar structure and the relative configuration of the isolated compounds were elucidated on the basis of modern chemical and spectroscopic methodes,such as ¹H NMR,¹³C NMR,2D-NMR,HR-ESIMS,etc.The absolute configuration of the isolated compounds were elucidated by X-ray crystallography and comparison of their experimental and calculated CD data.Totally,28 compounds were isolated and elucidated from the the ethyl acetate extract of Carpesium abrotanoides L.They were caroguaianolide A（1）,caroguaianolide B（2）,caroguaianolide C（3）,caroguaianolide D（4）,caroguaianolide E（5）,akihalin（6）,4β-hydroxy,10β-hydroperoxyl,5αH,7αH,8βH-guaia-1,11（13）-dien-8α,12-olide（7）,4α-hydroxy-9β,10β-epoxy-1βH,5αH-guaia-11（13）-en-8α,12-olide（8）,carabrolactone B（9）,4α-hydroxy-1βH-guaia-9,11（13）-dien-12,8α-olide（10）,（3aR,4aS,5S,7aS,8S,9aR）-5-hydroxy-4a,8-dimethyl-3-methylen-decahydroazuleno[6,5-b]furan-2（3H）-on（11）,2-desoxy-4-epi-pulchellin（12）,8-epi-inuviscolide（13）,inuviscolide（14）,granilin（15）,telekin（16）,isoalantolactone（17）,3α,5α-dihydroxyisoalantolactone（18）,isotelekin（19）,asperilin（20）,11（13）-dehydroivaxillin（21）,carabrone（22）,carabrol（23）,postiasecoguaianolide（24）,7,8-epoxy-9-（isobutyryloxy）thymolisobutyrate（25）,10-Hydroxy-8,9-dioxyisopropylidenethymol（26）,luteolin（27）,amentoflavone（28）,including 5 new compounds（1-5）.Among the 28compounds,there are 24 sesquiterpenes（1-24）,2 monoterpenes（25-26）,2 flavonoids（27-28）,and 19 compounds were isolated from Carpesium abrotanoides L for the first time.All the sesquiterpenes were evaluated in vitro for their cytotoxic activities against 8human cancer cell lines（Ca Ski,CNE2,HepG2,SH-SY5Y,HGC-27,MDA-MB-231,A549,Caco-2）using the MTT assay method.Compound 10 showed significant cytotoxic activities against MDA-MB-231,HGC-27 and Caco-2 cancer cell line with the IC₅₀ values of 4.07μM,8.95μM and 21.42μM.