Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.
University of Chinese Academy of Sciences, Beijing 100039, China.
Mar Drugs. 2020 Nov 20;18(11):576. doi: 10.3390/md18110576.
Three new acylated aminooligosaccharide (-), along with five known congeners (-), were isolated from the marine-derived sp. HO1518. Their structures were fully elucidated by extensive spectroscopic analysis, mainly based on 1D-selective and 2D TOCSY, HSQC-TOCSY, and HRESIMS spectrometry measurements, and by chemical transformations. All of the compounds were evaluated for their α-glucosidase and pancreatic lipase inhibitory activities. Among the isolates, 6--isobutyryl-acarviostatin II03 () and 6--acetyl-acarviostatin II03 (), sharing acarviostatin II03-type structure, showed the most potent α-glucosidase and lipase inhibitory effects, far stronger than the antidiabetic acarbose towards α-glucosidase and almost equal to the anti-obesity orlistat towards lipase in vitro. This is the first report on inhibitory activities against the two major digestive enzymes for acylated aminooligosaccharides. The results from our investigation highlight the potential of acylated aminooligosaccharides for the future development of multi-target anti-diabetic drug.
从海洋来源的 sp. HO1518 中分离得到了三种新的酰化氨基寡糖 (-)，以及五种已知的同系物 (-)。通过广泛的光谱分析，主要基于 1D-选择性和 2D TOCSY、HSQC-TOCSY 和 HRESIMS 光谱测量以及化学转化，充分阐明了它们的结构。所有化合物均评估了其对 α-葡萄糖苷酶和胰脂肪酶的抑制活性。在分离得到的化合物中，6--异丁酰基-acarviostatin II03 () 和 6--乙酰基-acarviostatin II03 ()，具有 acarviostatin II03 型结构，表现出最强的 α-葡萄糖苷酶和脂肪酶抑制作用，比抗糖尿病阿卡波糖对 α-葡萄糖苷酶的抑制作用强得多，几乎与抗肥胖奥利司他对脂肪酶的抑制作用相当。这是酰化氨基寡糖对两种主要消化酶的抑制活性的首次报道。我们的研究结果强调了酰化氨基寡糖在未来开发多靶点抗糖尿病药物方面的潜力。
