Synthesis Of Derivatives Of 8-Aminomethylluteolin And Their Anti-inflammatory Activity

The relationship between chemical structure and bioactivity of drugs is important in the research of new drugs. Analyzing the structure and active mechanism of natural active compounds can direct theoretically the development of new drugs to be more rational and effective.Non-steroidal anti-inflammatory drugs(NSAIDs) are the clinically common anti-inflammatory agents, and the present NSAIDs usually lead gastrointestinal and hepatonephric damage. Therefore, it is a significant subject to exploit new NSAIDs of good antiinflammatory activity and weak side-effct.Luteolin belonging to four hydroxys substituted flavones is widely distributed in the plant kingdom and possesses various biological activities and pharmacological properties. Some pharmacological tests and clinical observations show that luteolin has antibiotic, antiviral, antihypercholesterolemic and antitumor activities, which arose many chemists and pharmocologists interested in the research of luteolin. Natural luteolin has been clinically utilized to relieve cough, expel Phlegm and diminish inflammation, which has achieved good therapeutic effects.It is promising to ulilize luteolin as NSAIDs to cure chronic bronchitis.Mannich base exhibits a broad spectrum of bioactivities such as antitumor, anti-inflammatory, antischistosomal and antibacterial activities and various drugs obtained from Mannich reaction have proved more effective than their parent compounds. Otherwise, most NSAIDs contain aminomethyl groups and structural characteristics of their derivatives. The versatile ultility of the Mannich bases in pharmaceutical chemistry prompted us to introduce aminomethyl group into luteolin to produce more biologically active and less side-effect compounds. Ten new aminomethylation products were designed and synthesized via Mannch reaction,which were identified by ~1R, IH NMR and MS ( HRMS ) .Seven of the targeted compounds have been examined about their antiinflamm atory activity on xylene induced mice edema and the preliminary bioassay suggests that some of them exhibited potential anti-inflammatory activity. Comparison with the CMC group, especially, compound 2e,compound 2g and compound 2j have higer activity than luteolin. A detailed investigation into the bioactivities of these novel compounds is in progress.