Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents.

Abstract

The synthesis and biological evaluation of novel leonurine-SPRC conjugate, 3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1) is reported in this Letter. It is designed to improve the pharmacology efficiency by combining leonurine with S-propargyl-L-cysteine (SPRC), a cysteine analog, via a phenolic hydroxyl ester bond, which could be readily hydrolyzed to release bioactive leonurine and SPRC. Pharmacological evaluation has shown that 1 possesses potent cardioprotective effect against hypoxia-induced neonatal rat ventricular myocytes damage at lower molar concentration (10-fold less than leonurine required and 100-fold less than SPRC required). The mechanism is in partial related to improve hydrogen sulfide production, anti-oxidative stress and anti-apoptosis.

• Authors: Chunhua Liu, Xianfeng Gu, Yi Zhun Zhu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 23 Pg. 6942-6 (Dec 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20980147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Cardiotonic Agents
• Cross-Linking Reagents
• leonurine
• Gallic Acid
• Cysteine
• Hydrogen Sulfide

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Cardiotonic Agents (chemical synthesis, pharmacology)
• Cross-Linking Reagents
• Cysteine (chemistry)
• Gallic Acid (analogs & derivatives, chemistry)
• Hydrogen Sulfide (metabolism)
• Hypoxia (drug therapy, economics)
• Muscle Cells (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Rats