Highlights

• The study is the first to conduct a systematic structure-activity relationship (SAR) analysis of SCM-198 (Leonurine) for better cardioprotective effects.
• Compound 14o showed stronger cardioprotective activity than SCM-198 both in vitro and in vivo, at lower concentrations (1 μM, 10 μM).
• Pharmacokinetic profiling revealed improved bioavailability and metabolic stability of 14o compared to the original compound SCM-198.

Summary

The research article explores the design and synthesis of 35 novel analogs of SCM-198 (leonurine), a natural compound known for its cardioprotective effects. Through systematic structural modifications and structure-activity relationship (SAR) studies, the researchers identified compound 14o as the most promising analog, exhibiting significantly stronger protective effects against myocardial infarction (MI) than the original SCM-198.

Compound 14o demonstrated enhanced cell viability in oxidative stress models, better preservation of mitochondrial function, and greater inhibitive effect of apoptosis-related markers such as Bcl-2 and caspase-3. In vivo tests using a mouse MI model confirmed that 14o significantly reduced infarct size and cardiomyocyte apoptosis, outperforming SCM-198.

Additionally, pharmacokinetic studies revealed that 14o has improved bioavailability and metabolic stability, making it a strong candidate for further development as a cardioprotective agent.

S. Luo, S. Xu, J. Liu, F. Ma, and Y. Z. Zhu, “Design and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations,” European Journal of Medicinal Chemistry, vol. 200, p. 112469, Aug. 2020, doi: 10.1016/j.ejmech.2020.112469.