Article

Leonurine-cysteine analog conjugates as a new class of multifunctional anti-myocardial ischemia agent.

Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai 201203, China.
European Journal of Medicinal Chemistry (Impact Factor: 3.43). 06/2011; 46(9):3996-4009. DOI: 10.1016/j.ejmech.2011.05.073
Source: PubMed

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.

0 Bookmarks
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: 1. Herba Leonuri, a traditional Chinese medicine, has a long history of development and application in China. In particular, Herba Leonuri has been widely used in the treatment of gynaecological and obstetric disorders for thousands of years. Recent studies have shown that Herba Leonuri has many different effects. 2. Herba Leonuri contains several active components, including alkaloids, flavonoids, diterpenes compounds and fatty acids. Recent studies have shown that these molecules exert beneficial effects in coronary artery disease and cerebral ischaemia. Thus, these molecules may become novel candidates for drug discovery and development. 3. The present review provides an overview of the chemical composition, with a focus on biological activity, of Herba Leonuri to stimulate new studies on traditional Chinese medicine.
    Clinical and Experimental Pharmacology and Physiology 03/2012; 39(3):274-82. · 2.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multifunction compounds (MFCs), designed as hybrid/conjugated or chimeric drugs have emerged as magic bullets in treatment of multifactorial diseases such as atherosclerosis, Alzheimer's diseases, osteoarthritis, diabetic complications and malaria.
    European Journal of Medicinal Chemistry 06/2014; 76:31–42. · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rearrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p-hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii rearrangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of to p-hydroxyphenyl acetic acid () using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 31 ns with a rate for appearance of of k = 7.1 × 10(6) s(-1) in aq. acetonitrile (1 : 1 v : v). These studies establish that the primary rearrangement pathway for involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of as an esterification and etherification reagent with a variety of substituted α-diazo-p-hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates.
    Photochemical and Photobiological Sciences 12/2013; · 2.92 Impact Factor