摘要
目的设计合成系列多羟基苯甲醛席夫碱,初步测定其对α-葡萄糖苷酶的抑制活性。方法以羟基取代苯甲醛及芳香胺为原料,采用微波辅助合成法合成多羟基苯甲醛席夫碱,并对目标化合物进行α-葡萄糖苷酶抑制活性实验。结果合成了18个目标化合物,其结构均经红外光谱及核磁共振氢谱确证,化合物2、3、4、8、13、14、15、16为已知化合物,其余10个化合物为新化合物。结论所合成的目标化合物具有较强的α-葡萄糖苷酶抑制活性,其中3-羟基苯胺-3,4-二羟基苯甲醛席夫碱(10)、3-羟基苯胺-2,4,6-三羟基苯甲醛席夫碱(12)、苯胺-2,4-二羟基苯甲醛席夫碱(15)的α-葡萄糖苷酶抑制活性均强于参照物白藜芦醇(IC50=23.9μmol.L-1),它们的IC50值分别为8.93、4.69、8.59μmol.L-1。酶抑制动力学实验表明该系列化合物为α-葡萄糖苷酶的非竞争性抑制剂。
α-Glucosidase inhibitor plays an important part in diabetes treatment and resveratrol was reported to possess α-glucosidase inhibitory activity.Structurally,polyhydroxybenzaldehyde Schiff bases are similar to resveratrol,except that the double bond CN is replaced by CC bond.Thus,polyhydroxybenzaldehyde Schiff bases may also be potent α-glucosidase inhibitors.In order to find better α-glucosidase inhibitors,eighteen polyhydroxybenzaldehyde Schiff bases which had similar molecular structures with resveratrol were synthesized.Among them,2,3,4,8,13,14,15,and 16 were reported previously,others were novel compounds.In this paper,target compounds were synthesized by microware-assisted one step coupling between six kinds of hydroxy-substituted benzaldehydes and three arylamines,respectively.The solventless reaction of hydroxy-substituted benzaldehyde and arylamine in presence of diatomite with 700 W power of household microwave oven gave the expected compounds in good yields.After dissolving the mixture in ethanol,concentration,recrystallization and drying,the target compounds were gathered.Their structures were confirmed by IR and 1H-NMR.The α-glucosidase inhibitory activity of the target compounds was evaluated and the result demonstrated that most of them had relatively remarkable α-glucosidase inhibitory activity than resveratrol（IC50=23.9 μmol· L-1）.Among all these compounds,10,12 and 15 were found to be the most potent α-glucosidase inhibitor with the IC50 value of 8.93,4.69 and 8.59 μmol· L-1.In addition,these compounds were found as noncompetitive inhibitors through the kinetic analysis.The result also showed that target compounds synthesized from 2,4-or 3,4-hydroxy-substituted benzaldehyde had more potent inhibitory activity.
出处
《中国药物化学杂志》
CAS
CSCD
2011年第5期370-375,共6页
Chinese Journal of Medicinal Chemistry
基金
中山大学实验室开放基金项目(KF201027)
暨南大学广东省生物工程药物重点实验室开放基金项目
