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从内生真菌 GZWMJZ-288 中分离得到吲哚二萜衍生物。

Indole Diterpene Derivatives from the GZWMJZ-288, an Endophytic Fungus from .

机构信息

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.

出版信息

Molecules. 2023 Dec 4;28(23):7931. doi: 10.3390/molecules28237931.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35f1/10707737/5f118691c2ec/molecules-28-07931-g001.jpg

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