Synthesis Of Half-calycanthaceous Alkaloid Analogues And Determination Of Their Antibacterial And AchE Inhibitory Activities

The structure of Indole pyrrole is the key skeleton of Half-calycanthaceous alkaloid.They are modified to obtain different types of Half-calycanthaceous alkaloid analogues.These compounds have many biological activities,such as bacteriostasis and acetylcholinesterase.In this paper,indoleopyrrole skeleton was synthesized from 3-indole-acetonitrile,and 40 Half-calycanthaceous alkaloid analogues were synthesized by structural modification.The antibacterial activity and inhibition of acetylcholinesterase activity were preliminarily studied.Specific research contents include:1.The Half-calycanthaceous Alkaloid Analogues were synthesized from 3-indole-acetonitrile by oxidation,alkylation,reduction and acylation reaction.The structures of 40 synthesized compounds were characterized by 1H-NMR-13C-NMR.2.The antimicrobial activity of 40 synthetic compounds were determined by microdilution method.The results show that: The MIC of compound b8,b9 for Verticillium dahliae was 15.63,7.81 ?g/m L,which was better than chlorothalonil 31.25 ?g/m L;The MIC of compound a6,b7,b9,c7 for Curvularia,lunaia was 62.50 ?g/m L,which was better than that of carbendazim 250.00 ?g/m L and chlorothalonil 125.00 ?g/m L.The MIC of compound b14 for Fusarium oxysperium sp.vasinfectum was 62.50 ?g/m L,which was better than that of chlorothalonil 250.00 ?g/m L.The MIC of compound c2,c3,c3,c8 for Ralstonia.solanacearumwas 31.25 ?g/m L,which was better than that of gentamicin(62.50 ?g/m L)and streptomycin(250.00 ?g/m L).The MIC of compound a5,b8 against Candida krolimus was 31.25 ?g/m L,which was better than that of fluconazole(62.50 ?g/m L)and amphotericin B(250.00 ?g/m L).The inhibitory effect of compound a5 on Verticillium dahlia hypha was positively correlated with the concentration of the sample.The concentration was 31.25,62.50,125.00,250.00 g/m L,the inhibition rates of the mycelium were 46.24%,46.95%,63.44%,67.74 %..The inhibitory effect of compound c7 on Curvularia,lunaia was positively correlated with the concentration of the sample.The concentration was 62.50,125.00,250.00 ?g/m L,the inhibition rates of the mycelium were 15.50%,31.22%,77.73%.The concentration of compound c7 was 125.00 g/m L,the inhibition rate on the spore germination of Curvularia vularia hmaia was 76.23%.The concentration of compound c7 was 250.00 g/m L,the inhibition rate of mycelium biomass of Curvularia hmaia was 43.68%.The concentration of compound c8 was 500 ?g/m L,the inhibition rate on the spore germination of Candida krolimus could reach 87.46%.Compound c8 inhibited the growth curve of Ralstonia.solanacearum.The concentration of the sample was 500 ?g/m L,the growth of the bacterium was almost completely inhibited.3.Determination of Ach E activity of compounds by modified Ellman colorimetry,The results show that : The inhibition rate is dose dependent with the sample concentration.When the concentration of the sample is 1mg/m L,the inhibition rate of compounds a8,a9,b11,c4,c6,c13,c14 on Ach E is more than 80%.The IC50 values of compound c2,c11 were 0.01,0.13 ng/m L.