3-(4′-苯甲酰基氨基-苯基)-香豆素衍生物的合成及体外降血糖活性

胡玉恒; 孙捷; 杨洁; 王晓静

doi:10.11665/j.issn.1000-5048.20190206

3-(4′-苯甲酰基氨基-苯基)-香豆素衍生物的合成及体外降血糖活性

Synthesis and in vitro hypoglycemic activity of 3-(4′-benzoyl amino-phenyl)-coumarin derivatives

摘要

摘要: 首先以对氨基苯乙酸和水杨醛类化合物为原料，通过Perkin缩合反应，再经盐酸酸化合成了3个3-芳基香豆素类化合物 4a ~ 4c ；再与取代苯甲酰氯 6a ~ 6h 通过酰胺化反应合成得到了10个3-(4′-苯甲酰基氨基-苯基)香豆素类化合物 7a ~ 7j 。所有目标化合物的结构均经过¹H NMR，¹³C NMR，ESI-MS进行了确证。通过测定α-葡萄糖苷酶抑制活性和晚期糖基化终产物(AGEs)形成抑制活性评价了目标化合物的体外降血糖活性。结果表明化合物 7f (IC₅₀=10.84±0.36 μmol/L)表现出较好的α-葡萄糖苷酶的抑制活性；化合物 7g (IC₅₀=5.01±0.55 μmol/L)对AGEs形成抑制活性远高于阳性药氨基胍盐酸盐(AG，IC₅₀=290.31±7.32 μmol/L)，这些结果为抗糖尿病药物的进一步研究提供了理论基础。

Abstract: Firstly, three 3-arylcoumarins 4a- 4c were synthesized from p-aminophenylacetic acid and salicylaldehyde by Perkin condensation reaction and hydrochloric acid acidification; subsequent-amidation reaction of 4a- 4c with substituted benzoyl chlorides 6a - 6h furnished; ten 3-(4′-benzoyl amino-phenyl)coumarins 7a- 7j . The structures of all target compounds were fully characterised by NMR and ESI-MS. Those target compounds were screened for-glucosidase inhibitory and advanced glycation end products(AGEs)formation inhibitory activity. The results showed that compound 7f had good inhibitory activity against α-glucosidase(IC₅₀=10. 84±0. 36 μmol/L); compound 7g possessed much more potent inhibitory activity against AGEs formation(IC₅₀=5. 01±0. 55 μmol/L)than the positive control aminoguanidine hydrochloride(IC₅₀=290. 31±7. 32 μmol/L). These results provided a theoretical basis for further research on antidiabetic drugs.

HTML全文

参考文献(19)

施引文献

资源附件(0)