Design, Synthesis, and Study of Protective Activity Against Stroke for Novel Water-Soluble Aldehyde Dehydrogenase 2 Activators
Fengping Zhao, Zhenming Yu, Wei Tian, Xinhui Huang, Qingsen Zhang, Ruolan Zhou, Jian Hu, Shichong Yu, Xin Chen, Canhui Zheng
TL;DR
Researchers developed new water-soluble compounds that activate ALDH2, which may help treat stroke by reducing brain damage in animal models.
Contribution
The study introduces novel water-soluble ALDH2 activators with significantly improved solubility and efficacy for stroke treatment.
Findings
Compound D10 showed 114% activation of ALDH2 compared to Alda-1.
The hydrochloride salt D27 had over 200-fold increased water solubility.
Intravenous D27 reduced infarct area in rat stroke models.
Abstract
Stroke poses a serious threat to human health, while there are very few drugs that can directly alleviate ischemia/reperfusion injury and improve the prognosis. Studies have shown that small-molecule activators of aldehyde dehydrogenase 2 (ALDH2) have the potential to become novel therapeutic drugs for ischemic stroke. In this study, through the systematic structural optimization of novel N-benzylaniline-based ALDH2 activators obtained from our previous virtual screening, ALDH2 activators with improved water solubility and activity were obtained. Among them, compound D10 exhibits the best activity, with a maximum activation fold reaching 114% relative to Alda-1. And the water solubility of its hydrochloride salt D27 was increased by more than 200-fold. The intravenous injection of this compound can significantly reduce the infarct area in the rat model of cerebral infarction compared…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Figure 25
Figure 26
Figure 27
Figure 28
Figure 29
Figure 30
Figure 31
Figure 32
Figure 33
Figure 34
Figure 35
Figure 36
Figure 37
Figure 38
Figure 39
Figure 40
Figure 41
Figure 42
Figure 43
Figure 44
Figure 45
Figure 46
Figure 47
Figure 48
Figure 49
Figure 50Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsEicosanoids and Hypertension Pharmacology · Metabolomics and Mass Spectrometry Studies · Pharmacological Receptor Mechanisms and Effects