Studies On The Chemical Constituents Of Neem Seeds

Melia azedarach Linn.and Melia toosendan Sieb.et Zucc,timbers of Meliaceae family.Melia genus,grow mainly in Sichuan,Yunnan,Guizhou,Gansu,and other provinces of China.Their root barks have been used as traditional medicine in the country according to Chinese Pharmacopoeia.The efficacy of their fruits has a certain similarity.In some areas,fruits of M.azedarach can be used as a substitute for fruit of M.toosendan.Fruits of M.toosendan are widely studied by researchers,but the study of fruits of M.azedarach is less.Recently,the chemical constituents of Melia plants have been studied more and more deeply.In order to elucidate the active constituents and discover natural products with novel and diverse structure,we have investigated the chemical constituents of its fruits.Thirteen compounds of dichlorometheane fraction of ethanol extract were isolated,purified,and elucidated combining with various methods of isolation(silica gel,ODS,Sephadex LH-20,TLC,pre-HPLC)and structural elucidation(UV,IR,1D,2D NMR and HR-ESI-MS).Compounds 1,2 and 5?7 were C-seco limonoids,compounds 3 and 4 were havanensin limonoids,compounds 8?10 were pro-limonoids,compounds 11 was C-21 steroid,12 was vanillin and 13 was scopoletin.Among them,compounds 1?3 were new compounds.On the basis of isolation and elucidation work,the NO inhibitory activity(LPS-activated RAW 264.7 macrophages)of two new limonoids(compounds 1 and 3)with modified furan ring and two known compounds(compounds 5 and 6)were screened.The result of anti-inflammatory activity exhibited that a furan fragment isomerized limonoid compounds 3 had better anti-inflammatory activity with IC50 value at 37.41 M(positive drug:42.63 M).In our research,seven limonids were isolated from the fruits of M.azedarach.Among them,compounds 1?3 were new compounds.Biological activity screening found that a furan fragment isomerized limonoid compounds 3 had better anti-inflammatory activity.The results have enriched the varities and biological activities of limonids and laid the foundations for research and development for M.azedarach.