Synthesis And Activity Study Of Feruloyl Piperidine Compounds

BackgroundFerulic acid is a phenolic acid; it has the pharmacology activity of anti-oxidation,anti-inflammatory, anticancer, anti-mutation and radioprotective. Ferulic acid is widely used inmedicine, health products, cosmetics, food additives, and it is used in clinic practice toanticoagulant and antithrombotic. N element exists widely in all kinds of natural drugs andsynthetic compounds. Nitrogen-bearing six-member heterocyclic piperdine is an importanteffect of many drugs. From 1988 to 1998, about 12, 000 compounds containing a piperidinering became drug molecules or candidate drugs into clinical study. Based on the retention offerulic acid phenol and hydroxy groups of its analogues which have the antioxidant activity; aseries of feruloyl piperidine compounds through connected the carboxyl and piperidine intoamide were synthesized. We explored the pharmacological activity of these compounds.ObjectiveTo synthesize feruloyl piperidine compounds which have not been published before, andexplore the structure-activity relationships of these compounds to scavenge radical.MethodFerulic acid and its analogues as the materials via acetylation of phenolic hydroxyl,reacted with piperidine compounds into amide structure, and removed the acetyl to synthesizeferuloyl piperidine compounds. We determine d DPPH free-radical and OH free-radical clearingefficiencies via DPPH-Static Force Method and Ferrosin-Fe2+ Oxidation Method. Sinapoylpiperidine has the best activity to scavenge free radical in these feruloyl piperidine compounds;we used MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay to detectits influence on astrocyte.Results1. Ten new feruloyl piperidine compounds were successfully synthesized, and they wereidentified by IR 1HNMR and MS. 2. All synthesized compounds showed different levels activity in scavenging DPPH?and·OH . The activity of D1, D2, D4, D8, and D9 is better; D6, D10 is general; D3, D5, D7 ispoor.3. Sinapoyl piperidine can make astrocyte value-added. When sinapoyl piperidine withthe concentration of 0.1mmol/L was added, and cultivated the astrocyte for 24 hours or 48hours; they were obviously value-added. When sinapoyl piperidine with the concentration of0.01mmol/L was added, and cultivated the astrocyte for 24 hours; they were value-added.Conclusion1. A way to synthesize feruloyl piperidine compounds has been developed.2. The structure characteristics of feruloyl piperidine compounds have the same influenceon scavenging DPPH·and·OH. The structure-activity relationships are shown. 3,5-substitutedmethoxy and ethoxy on benzene ring can significantly enhance the free radical scavengingactivity. Nitro substituent on benzene ring obviously weaken such compounds scavenging freeradical activity, and bromine slightly reduce its activity. Methyl substituent on piperidine ringslightly weaken such compounds scavenging free radical activity.3. Sinapoyl piperidine can make astrocyte value-added.