(+)-Strebloside 及其衍生物与 Na/K-ATP 酶及其他靶点的相互作用。
Interaction of (+)-Strebloside and Its Derivatives with Na/K-ATPase and Other Targets.
机构信息
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
出版信息
Molecules. 2021 Sep 18;26(18):5675. doi: 10.3390/molecules26185675.
Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from , and some of its derivatives and Na/K-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein-protein interactions, Na/K-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents.
已研究了从中分离得到的细胞毒性强心苷（+）-strebloside 及其一些衍生物与 Na/K-ATPase 的对接构象。此外，还检查了（+）-strebloside 与其苷元，毛地黄毒苷，以及其他一些分子靶标（分别为 Nrf2 和 p53 的负调节剂 FIH-1、HDAC、KEAP1 和 MDM2），NF-κB，PI3K 和 Akt1 之间的结合，并将其与地高辛及其苷元地高辛进行了比较。结果表明，（+）-strebloside、地高辛及其苷元与 KEAP1 和 MDM2 结合，而（+）-strebloside、毛地黄毒苷和地高辛苷元与 PI3K 的活性口袋结合，（+）-strebloside 和地高辛与 FIH-1 相互作用。因此，这些强心苷可以直接靶向 HIF-1、Nrf2 和 p53 蛋白-蛋白相互作用、Na/K-ATPase 和 PI3K 来介导其抗肿瘤活性。总体而言，（+）-strebloside 似乎比地高辛更有希望开发潜在的抗癌药物。
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