ArticleScientific reports2016
Bioactivity Focus of α-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG.Disease models & mechanisms · 2019Article
- Yeast Models of Phosphomannomutase 2 Deficiency, a Congenital Disorder of Glycosylation.G3 (Bethesda, Md.) · 2019Article
- Conformational Differentiation of α-Cyanohydroxycinnamic Acid Isomers: A Raman Spectroscopic Study.Journal of Raman spectroscopy : JRS · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bioactivity focus on α-cyano-4-hydroxycinnamic acid (CHCA) scaffold results in a small library of novel multifunctional aldose reductase (ALR2) inhibitors. All the entities displayed good to excellent inhibition with IC50 72-405 nM. (R,E)-N-(3-(2-acetamido-3-(benzyloxy)propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (5f) was confirmed as the most active inhibitor (IC50 72.7 ± 1.6 nM), and the best antioxidant. 5f bound to ALR2 with new mode without affecting the aldehyde reductase (ALR1) activity, implicating high selectivity to ALR2. 5f was demonstrated as both an effective ALR2 inhibitor (ARI) and antioxidant in a chick embryo model of hyperglycemia. It attenuated hyperglycemia-induced incidence of neural tube defects (NTD) and death rate, and significantly improved the body weight and morphology of the embryos. 5f restored the expression of paired box type 3 transcription factor (Pax3), and reduced the hyperglycemia-induced increase of ALR2 activity, sorbitol accumulation, and the generation of ROS and MDA to normal levels. All the evidences support that 5f may be a potential agent to treat diabetic complications.
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