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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

胡玉恒, 孙捷, 杨洁, 王晓静. 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[J]. 中国药科大学学报, 2019, 50(2): 168-174. DOI: 10.11665/j.issn.1000-5048.20190206
引用本文: 胡玉恒, 孙捷, 杨洁, 王晓静. 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[J]. 中国药科大学学报, 2019, 50(2): 168-174. DOI: 10.11665/j.issn.1000-5048.20190206
HU Yuheng, SUN Jie, YANG Jie, WANG Xiaojing. Synthesis and in vitro hypoglycemic activity of 3-(4′-benzoyl amino-phenyl)-coumarin derivatives[J]. Journal of China Pharmaceutical University, 2019, 50(2): 168-174. DOI: 10.11665/j.issn.1000-5048.20190206
Citation: HU Yuheng, SUN Jie, YANG Jie, WANG Xiaojing. Synthesis and in vitro hypoglycemic activity of 3-(4′-benzoyl amino-phenyl)-coumarin derivatives[J]. Journal of China Pharmaceutical University, 2019, 50(2): 168-174. 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

基金项目: 山东省自然科学基金资助项目(No.ZR2018LH021)

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

  • 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.
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  • 刊出日期:  2019-04-24

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