title: Leonurine-cysteine analog conjugates as a new class of multifunctional anti-myocardial ischemia agent.
abstract: The design, synthesis and biological evaluation of novel Leonurine-cysteine analog conjugates 3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1a), 3,5-dimethoxy-4-(2-animo-3-allysulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1b) and 3,5-dimethoxy-4-(3-(2-chlorocarbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4-guanidino-butyl ester (2) were reported in this paper. We tested their effects on hypoxia-induced neonatal rat ventricular myocytes. Our data showed that all of them had cardioprotective effects. Both of 1a and 1b were able to modulate hydrogen sulfide production, and 1a possessed higher biological activity than 1b and 2, which indicated that there was positive correlation between conjugates and their precursors. Furthermore we illuminated that the cardioprotective mechanism of 1a were related to increase SOD and CAT activity, decrease MDA and ROS level, protect some cell organs and regulate apoptosis-associated genes and proteins expression (bcl-2 and bax) via the caspase-3 pathway in molecular level. These results indicated that 1a had the potential to be a new class of multifunctional anti-myocardial ischemia agent. Most importantly, these results provided us important clues for the further design and modification of this type of Leonurine-cysteine analog conjugates in future.
authors: Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai 201203, China.
authors: Chunhua
authors: C
authors: Liu
authors: Wei
authors: W
authors: Guo
authors: Xueru
authors: X
authors: Shi
authors: M A
authors: MA
authors: Kaium
authors: Xianfeng
authors: X
authors: Gu
authors: Yi Zhun
authors: YZ
authors: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000378:metabolism; D013058:Mass Spectrometry; D017202:Myocardial Ischemia / Q000188:drug therapy*; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C013587:leonurine; D008315:Malondialdehyde; D005707:Gallic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D003545:Cysteine