Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents.
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.
Liu
Chunhua
C
Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Gu
Xianfeng
X
Zhu
Yi Zhun
YZ
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003432:Cross-Linking Reagents; D003545:Cysteine / Q000737:chemistry*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006862:Hydrogen Sulfide / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy / Q000191:economics; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
D002316:Cardiotonic Agents; D003432:Cross-Linking Reagents; C013587:leonurine; D005707:Gallic Acid; D003545:Cysteine; D006862:Hydrogen Sulfide