Synthesis of Bioactive Natural Polymethoxyflavones and Their Vinyl Ether Derivatives

Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.

Efficacious anti-cancer property of flavonoids from citrus peels

Cancer is one of the two leading human fatal diseases.Drug development for cancer intervention has progressed well in past decades yet existing drugs face many limitations in applications and effectiveness and are often associated with serious of side effects,which can further deteriorate the patients’quality of life.Recent development of natural product based and therapeutically sound anti-cancer agents have gained popularity in the field of functional foods,in which a few have demonstrated efficacy and minimal toxicity toward the prevention and treatment of carcinogenesis.With multiple active molecular components,citrus peels and derived extracts have demonstrated potent efficacious properties against various cancers due in large part to the rich content of flavonoids present in citrus peels.This review summarizes the results of currently available data regarding the in vivo anti-cancer activity of citrus peel flavonoids,and identifies opportunities for subsequent human clinical trials to assess preventive and therapeutic effects in the near future.

5-Demethylnobiletin and its major metabolites:efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells

5-Demethylnobile tin(5-DMN),a hydroxylated polymethoxyflavone(OH-PMF)identified in aged citrus peels,has demonstrated health benefiting effects in previous studies.5-DMN undergoes biotransformation in vivo,yielding 5,3’-didemethylnobiletin(5,3’-DDMN),5,4’-didemethylnobiletin(5,4’-DDMN)and5,3’,4’-tridemethylnobiletin(5,3’,4’-TDMN).However,the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear.In this study,an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites,and their molecular structures were confirmed by;H NMR and LC-MS.Cytotoxicity,cell cycle arrestment,apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells.The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner.Their anti-proliferative activity was exerted through inducing G2/M phase arrestment,cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3.Our results indicated that 5,3’-DDMN and5,3’,4’-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN,followed by 5,4’-DDMN.The expression of cleaved caspase-3 was the highest in cells treated with 5,4’-DDMN,implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins.Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.

Synthesis and Acetylcholinesterase Inhibitory Activity of Polymethoxyflavone Mannich Base Derivatives

A series of novel polymethoxyflavone Marmich base derivatives 1--8 was synthesized by Mannich reaction of 5-hydroxy-3,7,3＇,4＇-tetramethoxyflavone 9 with various secondary aliphatic amines and formaldehyde. Their acetylcholmesterase（AChE） inhibitory activities were evaluated. The results showed that most of them exhibited AChE inhibitory activity and especially piperidin-l-yl methyl substituent derivative 5（IC50=0.238 μmol/L） demon- strated stronger activity comparable with the positive control, neoeserinemethyl sulfate（IC50=1.39 μmol/L）, which is worthy of further development as an agent for Alzheimer＇s disease treatment.