State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
Natural Products Research Center of Guizhou Province, Guiyang 550014, China.
Molecules. 2023 Dec 4;28(23):7931. doi: 10.3390/molecules28237931.
A new indole diterpene, 26-dihydroxyaflavininyl acetate (), along with five known analogs (-) were isolated from the liquid fermentation of GZWMJZ-288, an endophyte from . The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds , , and have a good binding affinity with NPC1L1, among which compound exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound showed inhibitory activity against -glucosidase with an IC value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and -glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.
一种新的吲哚二萜,26-二羟基阿弗拉霉素乙脂(),以及五种已知的类似物(-),从内生真菌 GZWMJZ-288 的液体发酵中分离出来。这些化合物的结构通过 NMR、MS、化学反应和 X 射线衍射实验来确定。酶抑制活性筛选发现,化合物、和对 NPC1L1 具有良好的结合亲和力,其中化合物在 10 μM 的浓度下表现出比依折麦布更强的结合能力。此外,化合物对 -葡萄糖苷酶表现出抑制活性,IC 值为 29.22±0.83 μM,比阿卡波糖强 13 倍。这些结果表明,这些阿弗拉霉素类似物可能成为针对 NPC1L1 和 -葡萄糖苷酶的药物的先导化合物。通过计算机对接研究还研究了生物活性化合物与 NPC1L1 和 α-葡萄糖苷酶的结合模式。