SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives
Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure–activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could
confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 μM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model
with high predictive power (q2 = 0.741, r2 = 0.991).
Keywords: Cardiomyocytes protection; CoMFA model; MTT; PP1/GADD34 complex inhibitor; UPR; endoplasmic reticulum (ER) stress; eukaryotic translation initiation factor 2 subunit α (eIF2α) phosphorylation; predicted abilities; salubrinal; structure–activity relationships (SAR)
Document Type: Research Article
Publication date: 01 December 2012
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
- Editorial Board
- Information for Authors
- Subscribe to this Title
- Ingenta Connect is not responsible for the content or availability of external websites
Receive new issue alert- Access Key
- Free content
- Partial Free content
- New content
- Open access content
- Partial Open access content
- Subscribed content
- Partial Subscribed content
- Free trial content