Inactivation of viruses in platelet suspensions that retain their in vitro characteristics: comparison of psoralen-ultraviolet A and merocyanine 540-visible light methods

The ability of two fundamentally different photochemical procedures to inactivate model viruses in platelet suspensions was compared. Merocyanine 540 (MC 540) with visible light was used as an example of an oxygen-dependent chemical-directed at the viral membrane, and aminomethyl trimethyl psoralen (AMT) with ultraviolet A light (UVA) was used as an example of a nucleic acid-directed system. Antiviral conditions in petri dishes were identified and the effects of these procedures on platelet suspensions in plastic storage containers were studied. Concentrations of photochemicals in the 10 to 150 mumol range with 30 to 60 minutes of visible light (MC 540) or 1 to 2 minutes of UVA (AMT) readily inactivated 5 to 6 log10 of vesicular stomatitis virus (VSV) and other model viruses in platelet suspensions, provided the plasma concentration was reduced to about 15 percent by the use of a synthetic platelet storage medium. Extracellular pH, morphology scores, and aggregation response dropped markedly when platelets were treated with MC 540 and visible light. However, treatment with 136 mumol per L of AMT and 1 to 3 minutes of UVA could inactivate 5 log10 of VSV in platelet suspensions with retention of platelet characteristics for 4 days, particularly if oxygen levels were reduced during treatment. These studies demonstrate that AMT-UVA treatment meets the initial requirements for virus inactivation in platelet suspensions.     

圆果甘草三萜成分的研究

从河南产圆果甘草(Glycyrrhiza squamulosa Franch.)的根中分离鉴定了五个三萜类化合物,即白桦酯酸(betulinic acid,S-8)、马其顿酸甲酯(methyl ester of macedonic acid,S-9)、黄豆醇B(soyasapoge nol B,S-10)、齐墩果13(18)-烯-22α-氯-3β,24-二醇(olean-13(18)-ene-22α-Cl-3β,24-diol,S-12)和圆果皂甙元(squasapogenol.S-11),均为首次从该植物中获得,其中S-10为首次在甘草属中发现,S-12为酸水解转变物,S-11是一个新的五环三萜类皂甙元,经光谱解析确定其结构为齐墩果-11,13(18)-二烯-3β,22β-二醇(olean-11,13(18)-diene-3β,22β-diol)。     

3-甲基芬太尼衍生物立体异构体的 QSAR 研究

用比较分子力场分析(CoMFA)方法研究了3-甲基芬太尼和羟甲芬太尼立体异构体的三维定量构效关系(3D-QSAR)。所得CoMFA-QSAR模型有很好的预测能力(γ²_{cros-validated}=0.716,n_{optimalcomponent}=5,γ²_conventional=0.999,s=0.052,F=1305.1),模型中,被研究化合物的构象可能就是其活性构象。以AM1方法进行量子化学计算,获得上述可能活性构象的结构参数及空间位置参数。基于这些参数,用偏最小二乘法(PLS)获得了被研究化合物的QSAR方程。所得PLS-QSAR模型具有较好的预测能力,并且显示被研究化合物的镇痛活性取决于分子中负电性的哌啶氮原子(N_PA)净电荷以及哌啶氮原子、羰基氧原子、1-β-苯环、4-N-苯环、3-甲基和2′-羟基的空间位置。     

Vitamin K-dependent carboxylase

The conformational analysis of four glutamic acid analogues containing a cyclopentyl or cyclohexyl ring, substituted in position 1 by a Boc-protected amino group and a methyl ester group and in position 3 by a free carboxylate group (6–9), has been carried out in an aqueous environment, by ¹H and ¹³C NMR spectroscopy, and molecular dynamics (MD). These compounds have been shown to be weak competitive inhibitors (K_i? 20–65 mM) of the vitamin K-dependent carboxylation of Boc-Glu-OMe in rat liver microsomes independently of their ring size and stereochemical features. However, the cyclic trans isomers have been found more active than the cis ones and Boc-trans-C5-OMe (9) is the most potent inhibitor in the series (cis and trans isomers are defined by the relative arrangement of the carboxyl functions). Such cyclic glutamyl derivatives may provide valuable informations on the preferred bioactive conformations of synthetic glutamyl substrates at the active site of the carboxylase. In aqueous solution, the Boc-cis- and trans-C6 esters exhibit chair conformations with exclusively equatorial and axial substituent positions, while the Boc-cis- and trans-C5 compounds may display envelope E or ‘twist’ T conformations with the substituents in the following positions. equatorial, axial and isoclinal. For each compound, the conformations resulting from NMR and MD data were analyzed and classified according to the dihedral angles %1 and %2, the distances of functional groups, and the spatial charge distribution involving the free carboxyl group. A reduced number of conformational families were found to be in qualitative agreement with NMR and MD data. These results are discussed in relation with the carboxylase inhibitory activity of the analogues, and a spatial disposition of the glutamyl side chain that could be recognized by the carboxylase is deduced. © Munksgaard 1997.     

作用于神经系统药物:吡啶并[1,2-a]嘧啶酮系列化合物的合成

加锡果宁(Ⅰ)是中药野花椒的成分之一,具有较强的镇痛作用和中枢抑制作用。为寻找低毒高效的类似物,我们曾对其进行结构改造,设计合成了系列化合物并进行了药理试验。前文报道的是在母核芳环上引入不同取代基而不改变母核结构,本文进一步对不同母核的类似物进行了合成及药理研究。