Abstract

In this study, new azabenzimidazole-bridged bis-coumarin compounds have been synthesized and screened for their pancreatic lipase inhibitory properties. All compounds showed a considerable lipase inhibitory potential with IC₅₀ values ranging from 0.67 ± 0.047 to 3.15 ±0.081 µM. Compound Nʹ,Nʹʹ-[(6-bromo-2-oxo-1Himidazo[4,5-b]pyridine-1,3-diyl)bis(1-oxoethane-2,1-diyl)]bis(8-methyl-2-oxo-2H-chromene-3-carbohydrazide) (IIIe) having methoxy group on coumarin ring and compound N',N''-[(6-bromo-2-oxo-1H-imidazo[4,5-b]pyridine-1,3-diyl)bis(1-oxoethane-2,1-diyl)]bis(6-chloro-2-oxo-2H-chromene-3-carbohydrazide) (IIIb) having –Cl atom on coumarin ring have the highest inhibitory effects. A molecular docking study was performed on the binding pose and affinity of synthesized compounds at the binding sites of lipase.

中文翻译：

---

新型氮杂苯并咪唑桥联双香豆素化合物的合成、胰脂肪酶抑制特性的研究以及对接研究

摘要

在这项研究中，合成了新的氮杂苯并咪唑桥联双香豆素化合物，并筛选了其胰腺脂肪酶抑制特性。所有化合物均表现出相当大的脂肪酶抑制潜力，IC ₅₀值范围为 0.67 ± 0.047 至 3.15 ±0.081 µM。化合物N ʹ ,N ʹʹ-[(6-溴-2-氧代-1 H咪唑并[4,5- b ]吡啶-1,3-二基)双(1-氧代乙烷-2,1-二基)]双( 8-甲基-2-氧代-2H-色烯-3-碳酰肼)( IIIe )在香豆素环上具有甲氧基和化合物N',N'' -[(6-溴-2-氧代-1H-咪唑[ 4,5- b ]吡啶-1,3-二基)双(1-氧代乙烷-2,1-二基)]双(6-氯-2-氧代-2H-色烯-3-碳酰肼)( IIIb )，具有香豆素环上的-Cl原子具有最高的抑制作用。对合成化合物在脂肪酶结合位点的结合姿势和亲和力进行了分子对接研究。