Song Li

Shenyang Pharmaceutical University, Feng-t’ien, Liaoning, China

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Publications (89)178.09 Total impact

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    ABSTRACT: A series of novel Heteroaryldihydropyrimidines (HAPs) derivatives were designed and synthesized as potent inhibitors of HBV capsid assembly. These compounds were prepared from efforts to optimize an earlier series of HAPs, and compounds Mo1, Mo7, Mo8, Mo10, Mo12, and Mo13 demonstrated potent inhibition of HBV DNA replication at submicromolar range.
    Bioorganic & medicinal chemistry letters. 07/2014;
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    ABSTRACT: Combining drugs with complementary mechanisms of action may contribute to improved hypertension control in diabetic patients. Advanced glycation end-product (AGE) breakers, a new class of candidate drugs targeting aging-related cardiovascular dysfunction, may be useful as novel adjuvant agents to improve the efficacy of diabetic hypertension (DH) treatment. This study evaluated the effects of alagebrium (ALT-711), an AGE breaker, combined with nifedipine, a Ca(2+) channel blocker, in a rat model of streptozotocin-induced DH. Compared with monotherapy, combination treatment significantly decreased systolic and diastolic blood pressure values, increased the pulse pressure, and decreased the coefficient of variation of the systolic blood pressure. Plasma biochemistry indicated that the concentrations of prostacyclin and nitric oxide were increased. Gene expression analysis showed significantly decreased prepro-endothelin-1expression in the aorta. These results reveal that alagebrium significantly improves the anti-hypertensive actions of nifedipine in a rat model of DH and suggest its potential use in the successful control of clinical DH.Hypertension Research advance online publication, 26 June 2014; doi:10.1038/hr.2014.98.
    Hypertension research : official journal of the Japanese Society of Hypertension. 06/2014;
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    ABSTRACT: A new three-component cyclization method is described involving two starting materials, ethyl 4-chloroacetoacetate and aldehydes, catalyzed by piperidine, acid, and iodine. Ten corresponding polysubstituted phthalides are formed with good yields (44–78%). A mechanism of the reaction is also proposed.
    Synthetic Communications 06/2014; 44(12). · 1.06 Impact Factor
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    ABSTRACT: Transition metal copper (Cu) can exist in oxidized or reduced states in cells, leading to cytotoxicity in cancer cells through oxidative stress. Recently, copper complexes are emerging as a new class of anticancer compounds. Here, we report that a novel anticancer copper complex (HYF127c/Cu) induces oxidative stress-dependent cell death in cancer cells. Further, transcriptional analysis revealed that oxidative stress elicits broad transcriptional changes of genes, in which autophagy-related genes are significantly changed in HYF127c/Cu-treated cells. Consistently, autophagy was induced in HYF127c/Cu-treated cells and inhibitors of autophagy promoted cell death induced by HYF127c/Cu. Further analysis identified that the MAPK11/12/13/14 (formerly known as p38 MAPK) pathway was also activated in HYF127c/Cu-treated cells. Meanwhile, the MAPK11/12/13/14 inhibitor SB203580 downregulated autophagy by inhibiting the transcription of the autophagy genes MAP1LC3B, BAG3 and HSPA1A, and promoted HYF127c/Cu-induced cell death. These data suggest that copper-induced oxidative stress will induce protective autophagy through transcriptional regulation of autophagy genes by activation of the MAPK11/12/13/14 pathway in HeLa cells.
    Autophagy 05/2014; 10(7). · 12.04 Impact Factor
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    ABSTRACT: Graphical abstract Figure optionsDownload full-size imageDownload as PowerPoint slide
    Bioorganic & Medicinal Chemistry Letters. 01/2014;
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    ABSTRACT: The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists.
    Molecules 01/2014; 19(3):3539-51. · 2.43 Impact Factor
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    ABSTRACT: A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-α production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-α release with an IC50 value of 0.033 μM, which is equipotent to that of BIRB796 (IC50 = 0.032 μM).
    Molecules 01/2014; 19(2):2004-2028. · 2.43 Impact Factor
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    ABSTRACT: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from three patients and was identified as H7N9 in China. The antiviral agents are required to treat the patients with the avian influenza H7N9 virus infection. In this study, we assessed the antiviral potential of oseltamivir, peramivir, favipiravir (T-705), amantadine and remantadine against novel reassortant avian-origin influenza H7N9 virus in vitro. All three avian influenza H7N9 virus strains were sensitive to oseltamivir, peramivir and favipiravir (T-705), but resistant to amantadine and rimantadine. These properties might be therapeutically advantageous if they are considered for possible clinical use to treat H7N9 virus infections.
    Antiviral therapy 08/2013; · 3.07 Impact Factor
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    ABSTRACT: It has been universally acknowledged that the increase in cardiac and vascular stiffness is due to the formation of advanced glycosylation end-products (AGEs). Research on the stable form of 3-(carboxymethyl)-4-methylthiazol bromide sodium salt (C6H7BrNNaO2S) showed that it had a notable effect on breaking the AGEs. Two compounds with novel structures, zwitterionic 3-(carboxymethyl)-4-methylthiazol (C6H7O2NS) and a dipolymer (C12H15O4N2S2Br) complex, were obtained. When compared with the forms of sodium salt and dipolymer, zwitterion had an obvious advantage in stability, solubility, synthesis and pH, which made the zwitterion a promising drug. The structure of sodium salt, dipolymer and zwitterion was comparatively analyzed by such methods as single crystal X-ray diffraction, ESI-MS, (1)H NMR, FT-IR and in situ IR.
    European journal of medicinal chemistry 08/2013; 68C:89-95. · 3.27 Impact Factor
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    ABSTRACT: We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets.
    Chinese Chemical Letters 08/2013; 24(8):715–718. · 1.18 Impact Factor
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    ABSTRACT: Effects of cannabinoid receptor 1 (CB1R) blockade were observed by comparing 9-day and 6-week SR141716 treatments in monosodium glutamate (MSG)-induced hypometabolic and hypothalamic obesity (HO) in rats for the first time and molecular mechanisms were investigated. Compared with normal rats, the MSG rats display typical symptoms of the metabolic syndrome, i.e., excessive abdominal obesity, hypertriglyceridemia, hyperinsulinemia, insulin resistance, and hepatic steatosis, but with lower food intake. Although both the 9-day and 6-week treatments with the specific CB1R antagonist SR141716 effectively lowered body weight, intraperitoneal adipose tissue mass, serum triglyceride (TG), and insulin level, the effect of chronic treatment is more impressive. Moreover, serum cholesterol, free fatty acids (FFA), fasted and postprandial blood glucose, and insulin insensitivity were more effectively improved by 6-week exposure to SR141716, whereas hypophagia was only effective within the initial 2 weeks. In addition, hepatic steatosis as well as hepatic and adipocyte morphology was improved. Western blot analysis revealed that the markedly increased CB1R expression and decreased insulin receptor (INR) expression in liver and adipose tissues were effectively corrected by SR141716. Consistent with this, deregulated gene expression of lipogenesis and lipolysis as well as glucose metabolic key enzymes were also restored by SR141716. In conclusion, based on present data we found that: (1) alteration of the hypothalamus in MSG rats leads to a lower expression of INR in crucially insulin-targeted tissues and hyperinsulinemia that was reversed by SR141716, (2) the abnormally increased expression of CB1R in liver and adipose tissues plays a vital role in the pathophysiological process of MSG rats, and (3) chronic CB1R blockade leads to a sustained improvement of the metabolic dysfunctions of MSG rats.
    Archiv für Experimentelle Pathologie und Pharmakologie 04/2013; · 2.15 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor γ (PPARγ) is a unique target for insulin sensitizer agents. These drugs have been used for the clinical treatment of type 2 diabetes for almost twenty years. However, serious safety issues are associated with the PPARγ agonist thiazolidinediones (TZDs). Selective PPARγ modulators (SPPARMs) which retain insulin sensitization without TZDs-like side effects are emerging as a promising new generation of insulin sensitizers. C333H is a novel structure compound synthesized by our laboratory. In diabetic rodent models, C333H has insulin-sensitizing and glucose-lowering activity comparable to that of TZDs, and causes no significant increase in body weight or adipose tissue weight in db/db mice. In diabetic db/db mice, C333H elevated circulating high molecular weight adiponectin isoforms, decreased PPARγ 273 serine phosphorylation in brown adipose tissue and selectively modulated the expression of a subset of PPAR γ target genes in adipose tissue. In vitro, C333H weakly recruited coactivator and weakly dissociated corepressor activity. These findings suggest that C333H has similar properties to SPPARMs and may be a potential therapeutic agent for the treatment of type 2 diabetes.
    Biological & Pharmaceutical Bulletin 04/2013; · 1.85 Impact Factor
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    ABSTRACT: A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 with low cytotoxicity.
    Molecules 01/2013; 18(5):5059-71. · 2.43 Impact Factor
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    ABSTRACT: An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis of their intermediates.
    Molecules 01/2013; 18(9):11144-52. · 2.43 Impact Factor
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    ABSTRACT: AbstractA series of tri‐substituted chiral pyrrolidin‐2‐one derivatives have been designed and synthesized as CC chemokine receptor 4 (CCR4) antagonists. The structure of CCR4 was built by homology modeling. Asymmetric synthesis was applied to synthesize the R,R configuration chiral pyrrolidin‐2‐one scaffold. The stereoisomeric configurations of the compounds were identified by 2D 1H‐1H COSY spectroscopy and 1D NOESY spectroscopy. This method was more economical and convenient than traditional X‐ray single crystal diffraction. In addition, the interactions between these compounds and the N‐terminal extracellular tail of CCR4 were studied using capillary zone electrophoresis. The CCR4 chemotaxis inhibition effect was tested in CCR4‐transfected HEK293 cells. Several compounds showed potent activities as CCR4 antagonists. Among these compounds, 1c is the most active one. Its apparent binding constant of CZE experiment result is (1.569±0.11)×105 L·mol−1, and its percentage inhibition of the HEK293/CCR4 cells migration with the concentration of 1 µmol·L−1 in DMSO is 59%. And compound 1f has slightly higher affinity to N‐terminal of CCR4 according to its apparent binding constant than 1b because of the introduced ester linkage. Further studies on the mechanism of these compounds are in progress.
    Chinese Journal of Chemistry 01/2013; 31(9). · 0.92 Impact Factor
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    ABSTRACT: Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure-activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 µM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model with high predictive power (q2 = 0.741, r2 = 0.991).
    Current Medicinal Chemistry 09/2012; · 3.72 Impact Factor
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    ABSTRACT: This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin (TM)- and hypoxia-induced apoptosis in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured from the ventricles of 1-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal (10, 20, and 40 µmol/L) for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS (high content screening) apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α) and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein (CHOP) was detected by immunocytochemistry. HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2α phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.
    Journal of Geriatric Cardiology 09/2012; 9(3):258-68.
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    ABSTRACT: IN THE TITLE COMPOUND [SYSTEMATIC NAME: (4R,4aS,7aR,12bS)-3-cyclo-propyl-meth-yl-4a,9-hy-droxy-7-oxo-2,3,4,4a,5,6,7,7a-octa-hydro-1H-4,12-methano-benzofuro[3,2-e]isoquinolin-3-ium bromide methanol monosolvate], C(21)H(26)NO(4) (+)·Br(-)·CH(3)OH, two of the three six-membered rings adopt chair conformations while the third, which contains a C=C double bond, adopts an approximate half-boat conformation. The 2,3-dihydro-furan ring adopts an envelope conformation. In the crystal, the components are linked by O-H⋯O and O-H⋯Br hydrogen bonds. The absolute stereochemistry was inferred from one of the starting materials.
    Acta Crystallographica Section E Structure Reports Online 03/2012; 68(Pt 3):o827. · 0.35 Impact Factor
  • Yan Liu, Wu Zhong, Song Li
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    ABSTRACT: A short and efficient synthesis of (Z)-2-substituted-5-(4-((2-substitued-5-oxoimidazolidin-4-ylidene)methyl)benzamido)benzoic acid derivatives (8a–g) as potential type of FabH inhibitors is described. Their structures were confirmed by MS, NOE and 1H NMR.
    Chinese Chemical Letters 02/2012; 23(2):133–136. · 1.18 Impact Factor
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    ABSTRACT: A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b was proven to be a potent CCR4 antagonist that can block cell chemotaxis induced by macrophage-derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and CKLF1, the natural ligands of CCR4. In addition, compound 6b is more effective than budesonide in the murine rhinitis model. The intravenous injection LD₅₀ of compound 6b is 175 mg/kg and the oral LD₅₀ is greater than 2,000 mg/kg.
    Molecules 01/2012; 17(8):9961-70. · 2.43 Impact Factor

Publication Stats

216 Citations
178.09 Total Impact Points

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Institutions

  • 2006–2014
    • Shenyang Pharmaceutical University
      • School of Pharmaceutical Engineering
      Feng-t’ien, Liaoning, China
    • University of Illinois, Urbana-Champaign
      Urbana, Illinois, United States
    • University of Southern California
      Los Angeles, California, United States
  • 2012
    • Beijing Institute of Microbiology and Epidemiology
      Peping, Beijing, China
  • 2009–2012
    • Government of the People's Republic of China
      Peping, Beijing, China
    • Jilin University
      • Department of Pharmacy
      Yung-chi, Jilin Sheng, China
  • 2001–2009
    • Academy of Military Medical Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2008
    • Sichuan University
      Hua-yang, Sichuan, China
  • 2006–2007
    • Beijing FivePlus Molecular Medicine Institute
      Peping, Beijing, China
  • 2003
    • National Center of Biomedical Analysis
      Peping, Beijing, China