| Natural flavonoids were popular for the biological activities of antioxidant, antivirus, antitumor and so on. At present, study of isolation, elucidation, structure modification and physiological activities of flavonoids is one of focus topics in chemical and medical fields.Novel structures of prenylated flavonoids isolated from Cudrania genus have been reported and displayed anti-inflammatory, hepatorrotective, anti-peroxidation and anti-tumor activities. Cudrania cochinchinensis is one of a shrub of Cudrania genus. Its roots have been applied for the treatment of digestive apparatus tumor, especially gastric carcinoma, and were also used as Chinese folk medicine "Chuan-po-shi" against tuberculosis, gonorrhea, rheumatism, mumps, jaundice, boils, scabies, bruising, and dysmenorrhea. Cudrania cochinchinensis fruits had physiological effects for the treatment of shernia, dypepsia and urination. However, there were only a few of literatures reported the chemical components from roots of Cudrania cochinchinensis, and the fruits phytochemical constituents and its biological effect of this plant has not yet been investigated. To take full use of rich resources of this plant and compare the chemical components differences, the chemical constituents from Cudrania cochinchinensis roots and fruits were investigated systematically in this paper. Moreover, aboundant flavanones contained in peels of pomelo and citrus with effects of lower cholesterol, antimicrobial resistance, resistance to atherosclerosis, antioxidation, antitumor and so on. In order to enhance the pharmacological activities of natural flavanones and exploit antitumor medicines with effective effects and low toxicity, flavanones derivatives of oximes and hydrozones were synthesized using hesperitin and naringin as starting materials. In addition, the cytotoxity against human cancer cell SGC-7901of all synthesized compounds were also assayed by MTT method.1. Seventeen compounds including three xanthons, ten flavonoids, two triterpenes, one sterol and one phenolic were isolated from roots of Cudrania cochinchinensis by silica gel column and polyamide column chromatography. Sructures of the compounds were elucidated on the basis of spectral data (MS,1H-NMR,13C-NMR, HMBC and HSQC) and by the comparison of spectroscopic data with the reported values in the literatures. They are isocudraniaxanthone B (?-1),1,6,7-trihydroxy-4-(1,1-dimethylallyl)-3-methoxyxanthone (?-2), gerontoxanthones H (?-3), artocarpesin (?-4), cycloartocarpesin (?-5), cudraflavone A(?-6), naringenin (?-7), aromadendrin (?-8), kaempferol (?-9), morin (?-10), quercetin (?-11), kaempferol-7-O-?-Dglucopyranoside (?-12), quercetin-7-O-?-D-glucopyranoside (?-13),4-ethoxymethylphenol (?-14), B-sitosterol (?-15),(13?,14?,17a,20R)-lanosta-7,24-diene-3?-ol (?-16),13?,14?,17?,20R-lanosta-7,24-diene-3?-O-aceta (?-17). Among them, ?-2was a new prenylated xanthone,?-14was first founded in Morus family.2. The ethanol extract of Cudrania cochinchinensis fruits was separated by silica column chromatography, the structures were elucidated based on spectroscopic and X-ray diffraction. Five known benzopyranisoflavones were isolated and elucidated as genistein (?-19), alpinumisoflavone (?-20),4'-O-methylalpinmumisoflavone (?-21),4'-O-methylderrone (?-22), isoderrone (?-23). Compounds ?-22, ?-23were isolated from this genus for the first time and obtained two crystals of ?-21and ?-23. Crystal structures showed compound ?-21and ?-23belong to monoclinic system, space group for P2(1)/c,3D-supramolecular structures were accumulated by hydrogen bond, ?-? and van der waals force. Futhermore, using isoderrone as material, five new benzopyranylisoflavones (?-23a??-23e) were synthesised by the mothods of modification ?-23at5-OH and7-OH with methyl, ethyl and isopentene.3. Derivatives of hesperitin (?-2, ?-3) and naringenin (?-2??-9) were synthesized by the steps of hydrolysis, selective methylation, selective O-prenylation or substituted by other groups using natural hesperitin and naringin as starting materials. Three new E-hesperitin oximes (?-1a??-3a), six E-hesperitin oxime ethers (?-1b??-3c) and nine novel E-naringenin oximes (?-1a??-9a), thirteen E-naringenin oxime ethers (?-1b??-9c) were synthesiszed by reacting flavanone derivatives(?-1??-3, ?-1??-9) with hydroxylamine hydrochloride, methoxylamine hydrochloride and benzyloxygen amine hydrochloride respectively. The structures of these prducts were characterizated by IR,1H NMR,13C NMR and HR-ESI-MS. 4. Intermediate hesperitin hydrazone (?-4) and naringenin hydrazone (?-10) were generated by reactions of hydrolysis in acidic condition and then reacted with hydrazine hydrate using natural hesperitin (?-1) and naringin as starting materials. Novel twenty eight N-benzylidene flavanone hydrazones and analogues (?-4a??-4n, ?-10a??-10n) were synthesised by the reaction of ?-4and ?-10with various aldehydes respectively. The synthetic route have the advantages of easy availability of starting materials, simple operation and good activities. In addition, it also can provide a new way for further exploitation and utilization of natural flavanone resources and development of antineoplastic drugs.5. In vitro anti-tumor activities of xanthone, benzopyran isoflavones and isodrrrone derivatives were assayed against BEL-7404(human liver carcinoma) and SGC-7901(human gastric carcinoma) cell lines by MTT method. The results indicated that compounds ?-1, ?-3and ?-23displayed moderate anti-proliferative activity against human cancer cell line SGC-7901, and7-O-alkylation of isoderrone derivatives showed weaker activity than the parent compound. Meanwhile, the anti-proliferative activities of flavanone oximes (?-1a??-3c, ?-1a??-9b) were also investigated against SGC-7901. The results revealed that the cytotoxicity of flavanone oximes increased dramatically compared with its precursor. And the oxime group fused at C-4of flavanones was the key factor to anti-tumor activities. For example, compounds ?-1a, ?-2a, ?-3a, ?-7a, ?-9a showed obvious cytotoxicities. However, the inhibition activities were decreased significantly when converted oximes to oxime ethers. Moreover, the cytotoxity against human cancer cell SGC-7901of the synthesized N-Benzylidene flavanone hydrazones (?-4a??-4n, ?-10a??-10n) were also evaluated. The results showed N-Benzylidene hesperitin hydrazones displayed better activities than N-Benzylidene naringenin hydrazones. Compounds ?-4c, ?-4e, ?-4h, ?-4n had similar cytotoxicity to cisplatin's against SGC-7901, and the corresponding IC50values were10.6?M,6.9?M,9.8?M and9.6?M respectively.In conclusion, prenylated isoflavones were the main compoents in Cudrania cochinchinensis fruits from the present investigation. It is different with prenylated flavonoids isolated from roots of this plant. Furhtermore, some of falvanone oximes (twenty-nine new compounds) and N-Benzylidene flavanone hdrazone derivatives (twenty-eight new compounds) showed obvious activities against SGC-7901, the relationship between structure and biological activity could be helpful in designing more potent anti-cancer agents for therapeutic use. |
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