Study On Chemical Composition And Biological Activity Of Strophioblachia Fimbricalyx Based On Active Targeting

Strophioblachia fimbricalyx is a species of the genus Strophioblachia from Euphorbiaceae.There are two species of the genus in the world,mainly distributed in the tropical and subtropical regions of Asia.There is only one specie in China.In Thailand,the plant is used infolk medicine treat migraine,fever,and cancer.Previous phytochemical studies have found that there are many novel structural chemical components in this genus,including diterpenoids,phenanthrenone and flavone glycosides,which have various biological pharmacological activities such as antiplasmodial,antitumor,antibacterial activities.The genus is a kind of medicinal plant resource with high development value.According to the previous research of our group,we found that the main active ingredients were concentrated in the ethyl acetate extract.In order to further explore the pharmacodynamic basis of this plant,we selected the ethyl acetate extract,the chemical composition study and the corresponding pharmacological activity studies were carried out at the site.In our experiment,many chromatographic techniques such as silica gel column chromatography,Sephadex LH-20 gel column chromatography,MCI column chromatography,rapid medium pressure preparative column chromatography,semi-preparative HPLC,etc.were used to isolate and purify the medium and large polar parts of the ethyl acetate extract.The structures of nineteen compounds,according to the spectral data(IR,HREMS,UV,CD,MS,1D and 2D NMR),combined with their physical and chemical properties,then by comparison of literature datas,were identified as:strophiofimbrin A(1),strophiofimbrin B(2),strophioblin(3),fimbricalxyxanhydride C(4),fimbricalyxoid G(5),fimbricalyxoid E(6),fimbricalyxoid F(7),fimbricalyxlactone D(8),fimbricalyxoid C(9),fimbricalyxoid D(10),fimbricalyxanhydride B(11),trigoxyphin M(12),trigohowilol G(13),fimbricalyxinlignan A(14),fimbricalyxinlignan B(15),2-methoxy-4-(2-propenyl)phenyl β-D-glucopyranoside(16),1-O-β-D-glucopyranosyl-4-allylbenzene(17),trans-4-(1-propenyl)-phenol-β-D-glucopyranoside(18),epipinoresinol(19),syringaresinol(20),securigtran I(21),rel-(3R,3’S,4R,4’S)3,3’,4,4’-Tetrahydro-6,6’-dimethoxy[3,3’-bi-2H-benzopyran]-4,4’-diol(22),medioresinol(23),clemiscosin A(24),fraxidin(25),isofraxidin(26),scopoletin(27),isoscopoletin(28),dibutyl terephthalate(29),syringaldehyde(30),loliolide(31),(3-ethylphenyl)-1,2-ethanediol(32).Among them,compounds 1 and 2 are novel carbon skeleton compounds,compounds 4-7,14,15 are new compounds,compounds 8 is new natural compound.Compound 1-3 featuring unusual 5/6/7 and 5/6/5 ring systems among natural diterpenoids,respectively.In the biosynthetic pathway,the existance of phenanthrenone and cleistanthane diterpenoids natural products from Euphorbiaceae plants.1-2 were proposed to derive via ring opening,expansion,recyclization and rearrangement from cleistanthane norditerpenoids.3 is a derivative of its re-opening and rearrangement.More interestingly,1 and 2 exhibited both neuroprotective effects and cytotoxic activities.The anti-tumor activity of the isolated compounds was screened by CCK-8 method.The results showed that compounds 1,2,6-13 showed effective inhibition to A549 cells,HeLa cells and HepG2 cells.In addition,a preliminary structure-activity relationship between diterpenoids(1-3)and phenanthrenes(4-13)combining with molecular docking was carried out.