Recent advances of MDM2-p53 inhibitors / 药学学报

Protein-protein interactions (PPI) are involved in a variety of biological processes, including cell-to-cell interactions, metabolism and development control. The misregulation, post-translational modification and interference of PPI are related to a variety of human diseases, making the regulation of these interactions a very attractive field of drug discovery. In recent years, the interaction between MDM2 and p53 has become a research hotspot, which plays an important role in the treatment of tumors. But unfortunately there are no such inhibitors approved all over the world. In this view, recent advances of MDM2-p53 inhibitors were briefly described and its inhibitors with potential therapeutic activities in clinical studies were introduced.

The secondary metabolites from a mutant 3d10-01 derived from Penicilliumchrysogenum S-3-25 by diethyl sulfate mutagenesis / 国际药学研究杂志

Objective To investigate the secondary metabolites from diethyl sulfate(DES)mutant 3d10-01 derived from Peni-cillium chrysogenum S-3-25. Methods The secondary metabolites were isolated by multiple separation techniques,such as silica gel,Sephadex LH-20 column chromatography and HPLC. The structures of the compounds were determined by ESI-MS and NMR spectroscopic data. The antitumor activity was assayed by the MTT method. HPLC-UV analysis was used to determine if compounds 1-7 were newly produced by the mutant. Results Seven secondary metabolites,including methyl 2,4-dihydroxy-3,5,6-trimethylbenzo-ate(1),6-hydroxymethyl-2,2-dimethylchromanone(2),regiolone(3),(3S,4S)-3,4-dihydro-3,4,8-trihydroxy(2H)naphthalenone (4),cerebroside C(5),cerebroside D(6)and dankasterone A(7),were isolated from the fermentation products of the mutant 3d10-01. Compounds 1,4 and 7 showed strong inhibitory effects on the five tested cell lines,but 2,3 and 6 only exhibited the proliferation of HL-60 cells to some extent. Compounds 1-4 and 7 were newly produced by the mutant 3d10-01. Conclusion Compounds 1-7 are firstly isolated from P. chrysogenum. The inhibitory effects on certain tested antitumor cell lines of compounds 1-4,6 and 7 are report-ed for the first time.

Modification of novel oxazolidinone derivatives at C-5 side chain and their antibacterial activities / 药学学报

<p><b>AIM</b>To modify the C-5 side chains of the oxazolidinone derivatives and evaluate their in vitro antibacterial activities preliminarily.</p><p><b>METHODS</b>The title compounds were synthesized in 9 - 12 steps with the starting material 3-fluoroaniline and their in vitro antibacterial activities were examined by using Mueller-Hinton broth dilution method.</p><p><b>RESULTS</b>Thirty new compounds were designed and synthesized, in which eighteen novel title compounds were prepared and their structures were confirmed by 1H NMR and ESI-MS. Eleven compounds showed antibacterial activities to a certain extent, among them compounds 7a, 9a and 11a displayed promising activity.</p><p><b>CONCLUSION</b>Compounds 7a, 9a and 11a were worth further studying.</p>

Inhibitory effect of reinioside C on LOX-1 expression induced by ox-LDL / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of reinioside C (RC) on the expression of lectin-like oxidized low density lipoprotein receptor (LOX)-1 mRNA and LOX-1 protein induced by oxidized low density lipoprotein (ox-LDL) in cultured human umbilical vein endothelial cells (HUVEC).@*METHODS@#HUVECs were cultured with ox-LDL (50 mg/L) for 24 h in the absence or presence of RC (1, 3, and 10 micromol/L). The expressions of LOX-1 mRNA and LOX-1 protein were examined by RT-PCR and Western-blot.@*RESULTS@#Incubation with ox-LDL (50 mg/L) significantly raised the expression of LOX-1 mRNA and LOX-1 protein,which was concentration-dependent.@*CONCLUSION@#RC can inhibit the increased expression of LOX-1 mRNA and LOX-1 protein induced by ox-LDL in HUVECs.

Oxidative stress in nitroglycerin tolerance and treatment with 3,4,5,6-tetrahydroxyxanthone / 中南大学学报(医学版)

OBJECTIVE@#To determine the relationship between the nitroglycerin tolerance and the stimulation of radical oxygen species (ROS) production, and the therapeutical effect of 3,4,5,6-tetrahydroxyxanthone.@*METHODS@#Vasodilator responses to nitroglycerin were examined in the isolated thoracic aorta. The contents of ROS,and cGMP were determined in the cultured human umbilical vein endothelial cells.@*RESULTS@#3,4,5,6-tetrahydroxyxanthone could significantly reduce the inhibition of relaxation by nitroglycerin. 3,4,5,6-tetrahydroxyxanthone could significantly inhibit the ROS increase and increase the cGMP level.@*CONCLUSION@#Nitroglycerin tolerance is associated with the stimulation of ROS production,and the reversal of nitroglycerin tolerance with 3,4,5,6-tetrahydroxyxanthone is related to the reduction of ROS.

Effect of simvastatin on cardiac fibrosis in patients with essential hypertension / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH).@*METHODS@#Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function.@*RESULTS@#After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05).@*CONCLUSION@#Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.

Changes of myocardial fibrotic indices and its mechanism in patients with ischemic cardiomyopathy / 中南大学学报(医学版)

OBJECTIVE@#To investigate the myocardial fibrotic indices in patients with ischemic cardiomyopathy (ICM), and explore the mechanism of myocardial fibrosis.@*METHODS@#The concentration of serum procollagen type III aminoterminal peptide (P III P), procollagen type IV aminoterminal peptide (P IV P), lamnin (LN), and hyaluronic acid (HA), as well as plasma angiotension II (AngII), aldosterone (ALD), and transforming growth factor beta 1 (TGFbeta1) in 46 ICM patients and 37 normal controls were measured by radioimmunoassay (RIA). The correlations between the plasma levels of AngII, ADL, TGFbeta1, and serum levels of P III P, P IV P, LN, and HA were analyzed.@*RESULTS@#Compared with normal controls, the concentrations of serum P III P, P IV P, LN, HA, and plasma AngII, ADL, and TGfbeta1, significantly increased in ICM patients. AngII, ALD, and TGFbeta1 levels were positively correlated with the indices of myocardial fibrosis.@*CONCLUSION@#The myocardial fibrosis exists in ICM patients and the serum concentrations of P III P, P IV P, LN, and HA may be an indirect index of myocardial fibrosis. AngII, ADL, and TGFbeta1 levels play important roles in myocardial fibrosis.

Plasma level of myeloperoxidase is not elevated in patients with stable angina pectoris / 中华老年医学杂志

Objective To investigate the plasma level change of myeloperoxidase(MPO)in patients suffering from stable angina pectoris.Methods Five hundred and seventy three patients underwent elective coronary angiography in a bi-racial cohort study,which included 295 patients with stable angina peetoris(SAP)and 278 subjects served as control.Plasma level of MPO and traditional risk factors of coronary artery disease(CAD)were measured.Results MPO levels did not differ significantly between control group and SAP group[126.3(95.8-160.2)mg/L vs 123.6(97.4-150.0) mg/L P＞0.05].MPO levels were similar across ethnicity and gender[black male 119.6(94.8-146.9) mg/L,white male 124.6(99.9～154.6)mg/L,black female 124.0(93.3～152.3)mg/L and white female 127.5(95.3～159.8)mg/L],and were correlated positively with the levels ofⅦfactor(r= 0.251,P＜0.01),fasting plasma glucose(r=0.095,P＜0.05),triglyceride(r=0.186,P＜0.01), total cholesterol(r=0.081,P＜0.05),high-sensitivity C-reactive protein(r=0.123,P＜0.01) and fibrinogen levels(r=0.077,P＜0.01),negatively correlated with adiponectin level(r=-0.115, P＜0.01).Conclusions Plasma MPO level is not elevated in patients with SAP.This suggests that MPO is not a characteristic feature of SAP.There are also no significant relationships between different genders and between different ethnicities.