Study On Synthesis And Pharmacology Of 1-(5'-Bromo Feruloyl)-4-Benzyl Piperazine Hydrochloride Analogs

Ferulic acid is a phenolic anti-oxidant. Ferulic acid derivatives have the pharmacology activities of anti-oxidation, anti-inflammatory, inhibiting thrombocyte congregation, lowering blood sugar, anti-tumor, radiation inhibition. In our study, we modificated the structure of ferulic acid. The carboxylic acid was transformed into amide while the phenolic hydroxyl group was reserved to keep its anti-oxidation activity. A series of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthesized, and their pharmacology activities were evaluated.1. Synthesis of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogsObjective: To synthesize 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.Methods: 5'-bromo ferulic acid was synthesized through bromo substitute and Knoevenagel reaction.1-(5'-bromo feruloyl)-4-benzyl piperazine was prepared via acetylation of phenolic hydroxyl, oxalyl chloride exchange with acid, N-acylation, removing of acetyl.Finally the target compounds were synthesized by 1-(5'-bromo feruloyl)-4-benzyl piperazine salification with hydrochloric acid.Results: 9 novel 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs were synthe- sized. Their structures were identified by elemental analysis, 1HNMR, MS and IR.Conclusion: A synthesis route to prepare 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochlor- ide analogs was established.2. Hydroxyl radical scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogsObjective: To study hydroxyl radical(?OH) scavenging activities in vitro of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.Methods: The ?OH scavenging activities in vitro of target compounds,ferulic acid(FA) and L-ascorbic acid(Vc) were analysed through 1,10-phenanthroline-Fe2+ detection system. Then the ?OH clearance percentage(CL) were calculated. The ?OH maximum clearance percentage(CLmax) differences between the drugs were analysed by SNK test.Results: All target compounds showed marked ?OH scavenging activities in vitro and had obvious dose-effect relationships. L5 had the highest CLmax. L8 had the lowest CLmax. L1, L3, L5 and L7 had higher CLmax than FA and Vc. L1, L3, L5, L6 and L7 had higher CLmax than Vc.Conclusion: All target compounds showed marked ?OH scavenging activities in vitro. The activity was influenced by the type and location of the substitute on benzal benzene ring. 2-Cl, 3-Cl, 2-CH3, 4-CH3 and 3-OCH3 enhanced the activity. 3-CH3 did not change the activity. 2-OCH3 and 4-OCH3 reduced the activity.3. Ear swelling inhibition activities in rats of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs Objective: To study anti-inflammatory activities of 1-(5'-bromo feruloyl)-4-benzyl piperazine hydrochloride analogs.Methods: L5, ferulic acid and ibuprofen were prepared as suspensions. Swelling degrees and swelling inhibitions were calculated to evaluate the ear swelling inhibition in rats induced by croton oil mixture. The swelling degree differences between the drug groups and control were analysed by two side Dunnett test. The swelling inhibition differences between the drug groups were analysed by SNK test. Results: All measuring doses of L5,ferulic acid and ibuprofen had extremely marked ear swelling inhibition activities in rats. The sequences of swelling inhibition at each doses were the following. 100mg/kg, ibuprofen>ferulic acid>L5.200mg/kg, ibuprofen>L5>ferulic acid. 400mg/kg, L5≈ferulic acid>ibuprofen.Conclusion: All measuring doses of L5, ferulic acid and ibuprofen had anti-inflammatory activities.