萘酚喹衍生物的合成及体内抗疟活性评价

Synthesis and in vivo antimalarial activity of naphthoquine derivatives

目的通过对萘酚喹进行改造,以发现活性更高的抗疟药。方法用3-羟基丙胺、4-羟基丁胺、N-(2-氨基乙基)吗啉、3,5-二甲基哌啶、3,5-二甲基哌嗪替代萘酚喹特丁氨基,采用曼尼希反应与关键中间体7缩合,得到目标化合物,结构经1H-NMR和ESI-MS验证。采用4日抑制法对衍生物进行体内抗疟活性评价,计算ED50。结果合成的5个萘酚喹衍生物为新化合物,均未见报道。体内活性结果显示化合物8、9、11具有抗疟活性,其中化合物9的抗疟活性较好。结论萘酚喹的特丁氨基被不同的含氮六元环取代会影响化合物的体内抗疟活性。

Objective To discover new compounds with better bioactivity by modifing naphthoquine.Methods Modifications were executed by Mannich reaction at the lateral side chain with 3-hydroxypropylamine,4-hydroxybutylamine,N-（2-aminoethyl） morpholine,3,5-dimethylpiperidine,and 3,5-dimethypaperizidine.1H-NMR and ESI-MS were performed to certify the structures.All compounds were tested in vivo against parasite strains K173 using ′4-day inhibition assays′ and the ED50 was calculated.Results Five naphthoquine analogs were new compounds.Data indicated compound 8,9 and 11 showed anti-malarial activity and compound 9 exhibited greater antimalarial activity.Conclusion The antimalarial activity in vivo changes when N-tertbutyl amino of naphthoquine is replaced by different side chains.