Direct interference with Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound displayed the highest metabolic stability and showed notable Keap1-Nrf2 PPI inhibitory activities . effectively triggered Nrf2 activation and increased the protein and mRNA expression of Nrf2-regulated genes in H9c2 cells. Moreover, pre-treatment with was shown to mitigate LPS-induced damage to H9c2 cells, causing a marked decrease in the levels of inflammatory factors as well as reactive oxygen species (ROS). Furthermore, was also shown to be non-mutagenic in the Ames test. Overall, our findings suggest that may be a promising drug lead as a Keap1-Nrf2 PPI inhibitor for myocarditis treatment.
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| http://dx.doi.org/10.1080/14756366.2022.2124408 | DOI Listing |
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