Discovery of coumarin-derived imino sulfonates as a novel class of potential cardioprotective agents.

Abstract

The burst of reactive oxygen species (ROS) contributes to and exacerbates cardiac injury. Exogenous supplementation of antioxidants or upregulation of endogenous antioxidant defense genes should be the potential therapies for cardiovascular disease. Sixteen coumarin-derived imino sulfonates compounds were synthesized with the ability of attenuating oxidative stress directly by reducing intracellular ROS level via promoting Nrf2 pathway. The cell-based assays showed that most of the compounds had significant protective activity against H2O2-induced oxidative injury in H9c2 cells. Compound 5h with the highest activity and low cytotoxicity was demonstrated to remarkably remove the intracellular ROS accumulation by activating expressions of Nrf2 and its downstream antioxidant proteins (ie. HO-1 and NQO1), indicating a novel promising antioxidant and Nrf2 activator. Overall, these findings demonstrated that compound 5h could serve as a potential cardioprotective agent. Moreover, our study features developing new antioxidants and Nrf2 activators by introducing a sulfonyl group and nitrogen atom to the α,β-unsaturated carbonyl entity in coumarin, rather than adding new functional groups or active fragments to coumarin itself.

• Authors: Bo Wei, Jing Zhou, Jia-Jia Xu, Jing Cui, Feng-Feng Ping, Jing-Jing Ling, Ya-Jing Chen
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 184 Pg. 111779 (Dec 15 2019) ISSN: 1768-3254 [Electronic] France
• PMID: 31629165 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antioxidants
• Cardiotonic Agents
• Coumarins
• Imines
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Reactive Oxygen Species
• Sulfonic Acids
• coumarin

Topics

• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Cardiotonic Agents (chemical synthesis, chemistry, pharmacology)
• Cells, Cultured
• Coumarins (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Discovery
• Humans
• Imines (chemistry, pharmacology)
• Molecular Structure
• NF-E2-Related Factor 2 (antagonists & inhibitors, metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Structure-Activity Relationship
• Sulfonic Acids (chemistry, pharmacology)