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Compound targeting Keap1-Nrf2-ARE signal channel, preparation method and application thereof

A signaling pathway and compound technology, applied in the field of compounds targeting the Keap1-Nrf2-ARE signaling pathway, can solve problems such as efficacy and safety limitations, disruption of the Keap1-Nrf2-ARE signaling pathway, and disruption of Keap1

Active Publication Date: 2022-07-05
HUBEI UNIV
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Problems solved by technology

Existing Keap1-Nrf2-ARE signaling regulators directly covalently bind to Keap1 to cause damage to the structure of Keap1, which may cause irreversible damage to the Keap1-Nrf2-ARE signaling pathway, thus limiting its efficacy and safety

Method used

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  • Compound targeting Keap1-Nrf2-ARE signal channel, preparation method and application thereof
  • Compound targeting Keap1-Nrf2-ARE signal channel, preparation method and application thereof
  • Compound targeting Keap1-Nrf2-ARE signal channel, preparation method and application thereof

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Embodiment Construction

[0039] In order to make the purpose, technical solutions and advantages of the present application more clear, the present application will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application, but not to limit the present application. The reagents not described in detail and individually in this application are all conventional reagents and can be obtained from commercial sources; the methods not described in detail are all conventional experimental methods, which can be known from the prior art.

[0040] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present application.

[0041] Preparation of compounds of formula I or formula II

[0042] 1. Strain

[0043] The compounds represented by formula I or formula II disclosed in the examples of this ap...

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Abstract

The invention discloses a compound of a targeted Keap1-Nrf2-ARE signal channel, a preparation method and application of the compound of the targeted Keap1-Nrf2-ARE signal channel. The compound is obtained by co-culturing penicillium and aspergillus ochraceus and extracting and separating secondary metabolites in fermentation liquor of the penicillium and the aspergillus ochraceus. The compound not only has no toxic effect on nerve cells, but also has a protective effect on nerve cells damaged by oxidation. Specifically, the compound plays a role in protecting nerve cells through a targeted Keap1-Nrf2-ARE signal channel, and the compound realizes a regulation effect on the signal channel through a non-covalent binding mode of forming a hydrogen bond and a part of hydrophobic bonds by binding Keap1, so that not only can activated release of Nrf2 be realized, but also the structure of Keap1 can be prevented from being damaged, and the compound has a good application prospect. Therefore, the safety of the compound in targeting a Keap1-Nrf2-ARE signal channel is improved.

Description

technical field [0001] The present application relates to the technical field of Keap1-Nrf2-ARE signaling pathway, in particular to compounds targeting Keap1-Nrf2-ARE signaling pathway, preparation methods and applications thereof. Background technique [0002] Oxidative stress is crucial for all living systems, especially it is widely involved in the pathophysiological changes of the nervous system. For example, cerebral ischemia-reperfusion injury is an acute manifestation of oxidative stress, and chronic oxidative stress is neurodegeneration. an important cause of the development of sexually transmitted diseases. [0003] Keap1-Nrf2-ARE is the most important autoantioxidative stress pathway studied so far. Under physiological conditions, NF-E2-related factor 2 (Nrf2) binds to Kelch-like ECH-associated protein 1 (Keapl) in the cytoplasm, and binds it through Keapl protein. Anchored on the cytoskeleton composed of actin, so that it cannot enter the nucleus to exert transc...

Claims

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Application Information

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IPC IPC(8): C07D471/14A61P25/00A61K31/4985C12P39/00C12P17/18C12R1/80C12R1/66
CPCC07D471/14A61P25/00C12P39/00C12P17/182Y02A50/30
Inventor 胡琳珍童周肖雪洋孔璐琦胡天卉盘诗湘汪钰钏
Owner HUBEI UNIV
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